{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T16:20:36Z","timestamp":1793290836977,"version":"4.5.0"},"reference-count":172,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Mycobacterium tuberculosis infections continue to pose a significant global health challenge, particularly due to the rise of multidrug-resistant strains, random mycobacterial mutations, and the complications associated with short-term antibiotic regimens. Currently, five approved drugs target cell wall biosynthesis in Mycobacterium tuberculosis. This review provides a comprehensive analysis of these drugs and their molecular mechanisms. Isoniazid, thioamides, and delamanid primarily disrupt mycolic acid synthesis, with recent evidence indicating that delamanid also inhibits decaprenylphosphoryl-\u03b2-D-ribose-2-epimerase, thereby impairing arabinogalactan biosynthesis. Cycloserine remains the sole approved drug that inhibits peptidoglycan synthesis, the foundational layer of the mycobacterial cell wall. Furthermore, ethambutol interferes with arabinogalactan synthesis by targeting arabinosyl transferase enzymes, particularly embB- and embC-encoded variants. Beyond these, six promising molecules currently in Phase II clinical trials are designed to target arabinan synthesis pathways, sutezolid, TBA 7371, OPC-167832, SQ109, and both benzothiazinone derivatives BTZ043 and PBTZ169, highlighting advancements in the development of cell wall-targeting therapies.<\/jats:p>","DOI":"10.3390\/ph18010070","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T07:59:42Z","timestamp":1736409582000},"page":"70","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Targeting the Heart of Mycobacterium: Advances in Anti-Tubercular Agents Disrupting Cell Wall Biosynthesis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3402-186X","authenticated-orcid":false,"given":"Ahmad","family":"Diab","sequence":"first","affiliation":[{"name":"School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9599-8654","authenticated-orcid":false,"given":"Henry","family":"Dickerson","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2421-1825","authenticated-orcid":false,"given":"Othman","family":"Al Musaimi","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK"},{"name":"Department of Chemical Engineering, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"ref_1","unstructured":"O\u2019Neill, J. (2016). Tackling Drug-Resistant Infections Globally: Final Report and Recommendations, Wellcome Trust."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"415","DOI":"10.2147\/IDR.S287792","article-title":"Encouraging the development of new antibiotics: Are financial incentives the right way forward? A systematic review and case study","volume":"14","author":"Dutescu","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_3","unstructured":"Lobanovska, M., and Pilla, G. (2017). Focus: Drug development: Penicillin\u2019s discovery and antibiotic resistance: Lessons for the future?. Yale J. Biol. Med., 90."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/iub.1872","article-title":"The role of two-component systems in the physiology of Mycobacterium tuberculosis","volume":"70","author":"Kundu","year":"2018","journal-title":"IUBMB Life"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1054\/tube.2002.0328","article-title":"Is Mycobacterium tuberculosis a closer relative to Gram-positive or Gram\u2013negative bacterial pathogens?","volume":"82","author":"Fu","year":"2002","journal-title":"Tuberculosis"},{"key":"ref_6","first-page":"E9","article-title":"The history of tuberculosis: From the first historical records to the isolation of Koch\u2019s bacillus","volume":"58","author":"Barberis","year":"2017","journal-title":"J. Prev. Med. Hyg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1016\/j.ijid.2021.02.107","article-title":"Global Tuberculosis Report 2020\u2013Reflections on the Global TB burden, treatment and prevention efforts","volume":"113","author":"Chakaya","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Zhuang, L., Ye, Z., Li, L., Yang, L., and Gong, W. (2023). Next-generation TB vaccines: Progress, challenges, and prospects. Vaccines, 11.","DOI":"10.3390\/vaccines11081304"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.rppnen.2017.10.009","article-title":"New drugs and perspectives for new anti-tuberculosis regimens","volume":"24","author":"Tiberi","year":"2018","journal-title":"Pulmonology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1093\/jac\/dkr173","article-title":"Molecular basis and mechanisms of drug resistance in Mycobacterium tuberculosis: Classical and new drugs","volume":"66","author":"Palomino","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","unstructured":"World Health Organization (2020). WHO Consolidated Guidelines on Tuberculosis: Module 4: Treatment: Drug-Resistant Tuberculosis Treatment: Online Annexes, World Health Organization."},{"key":"ref_12","unstructured":"Geiter, L. (2000). Ending Neglect: The Elimination of Tuberculosis in the United States, National Academies Press."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5009","DOI":"10.1021\/ja00122a038","article-title":"Studies on the mechanism of action of isoniazid and ethionamide in the chemotherapy of tuberculosis","volume":"117","author":"Johnsson","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11919","DOI":"10.1073\/pnas.93.21.11919","article-title":"The embAB genes of Mycobacterium avium encode an arabinosyl transferase involved in cell wall arabinan biosynthesis that is the target for the antimycobacterial drug ethambutol","volume":"93","author":"Belanger","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14729","DOI":"10.1074\/jbc.M700271200","article-title":"Identification of a novel arabinofuranosyltransferase AftB involved in a terminal step of cell wall arabinan biosynthesis in Corynebacterianeae, such as Corynebacterium glutamicum and Mycobacterium tuberculosis","volume":"282","author":"Seidel","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1093\/femsre\/fuz016","article-title":"Cell wall peptidoglycan in Mycobacterium tuberculosis: An Achilles\u2019 heel for the TB-causing pathogen","volume":"43","author":"Maitra","year":"2019","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Crellin, P.K., Brammananth, R., and Coppel, R.L. (2011). Decaprenylphosphoryl-\u03b2-D-ribose 2\u2032-epimerase, the target of benzothiazinones and dinitrobenzamides, is an essential enzyme in Mycobacterium smegmatis. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0016869"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.drudis.2008.09.004","article-title":"New anti-tuberculosis drugs in clinical trials with novel mechanisms of action","volume":"13","author":"Rivers","year":"2008","journal-title":"Drug Discov. Today"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr6901a1","article-title":"Guidelines for the treatment of latent tuberculosis infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020","volume":"69","author":"Sterling","year":"2020","journal-title":"MMWR. Recomm. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1136\/archdischild-2016-310870","article-title":"Tuberculosis (NICE clinical guideline 33)","volume":"102","author":"Turnbull","year":"2017","journal-title":"Arch. Dis. Child.-Educ. Pract."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"99","DOI":"10.5582\/ddt.2022.01025","article-title":"Prospects of contezolid (MRX-I) against multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis","volume":"16","author":"Yang","year":"2022","journal-title":"Drug Discov. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Daff\u00e9, M., and Marrakchi, H. (2019). Unraveling the structure of the mycobacterial envelope. Microbiol. Spectr., 7.","DOI":"10.1128\/microbiolspec.GPP3-0027-2018"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9554","DOI":"10.1021\/acs.chemrev.1c00043","article-title":"Chemical synthesis of cell wall constituents of Mycobacterium tuberculosis","volume":"121","author":"Holzheimer","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1111\/j.1574-6976.2008.00104.x","article-title":"Cytoplasmic steps of peptidoglycan biosynthesis","volume":"32","author":"Barreteau","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39524","DOI":"10.1074\/jbc.M112.390765","article-title":"Substrate-bound crystal structures reveal features unique to Mycobacterium tuberculosis N-acetyl-glucosamine 1-phosphate uridyltransferase and a catalytic mechanism for acetyl transfer","volume":"287","author":"Jagtap","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1107\/S0907444909001036","article-title":"Structure and function of GlmU from Mycobacterium tuberculosis","volume":"65","author":"Zhang","year":"2009","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, S., Kang, J., Yu, W., Zhou, Y., Zhang, W., Xin, Y., and Ma, Y. (2012). Identification of M. tuberculosis Rv3441c and M. smegmatis MSMEG_1556 and essentiality of M. smegmatis MSMEG_1556. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042769"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1099\/00221287-145-11-3177","article-title":"Alteration of a single amino acid residue reverses fosfomycin resistance of recombinant MurA from Mycobacterium tuberculosis","volume":"145","author":"Kempsell","year":"1999","journal-title":"Microbiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.resmic.2014.01.004","article-title":"Characterization of mycobacterial UDP-N-acetylglucosamine enolpyruvyle transferase (MurA)","volume":"165","author":"Xu","year":"2014","journal-title":"Res. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.tube.2009.10.007","article-title":"ATP-dependent MurE ligase in Mycobacterium tuberculosis: Biochemical and structural characterisation","volume":"90","author":"Basavannacharya","year":"2010","journal-title":"Tuberculosis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"16264","DOI":"10.1021\/bi961872+","article-title":"Kinetic mechanism of the Escherichia coli UDPMurNAc-tripeptide D-alanyl-D-alanine-adding enzyme: Use of a glutathione S-transferase fusion","volume":"35","author":"Anderson","year":"1996","journal-title":"Biochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/S0021-9258(20)74044-5","article-title":"The separation of lipoid fractions from tubercle bacilli","volume":"74","author":"Anderson","year":"1927","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1016\/S0040-4039(01)84131-9","article-title":"Studies on the mycolic acids from human tubercle bacilli","volume":"7","author":"Minnikin","year":"1966","journal-title":"Tetrahedron Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1017\/S0031182016002377","article-title":"Mycobacterial cell wall biosynthesis: A multifaceted antibiotic target","volume":"145","author":"Abrahams","year":"2018","journal-title":"Parasitology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/1574-6968.12597","article-title":"Crucial components of mycobacterium type II fatty acid biosynthesis (Fas-II) and their inhibitors","volume":"360","author":"Duan","year":"2014","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1517\/13543776.17.3.315","article-title":"Mycolic acids for the control of tuberculosis","volume":"17","author":"Sekanka","year":"2007","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1128\/CMR.18.1.81-101.2005","article-title":"Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis","volume":"18","author":"Takayama","year":"2005","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1111\/j.1365-2958.2007.05761.x","article-title":"The Mycobacterium tuberculosis FAS-II condensing enzymes: Their role in mycolic acid biosynthesis, acid-fastness, pathogenesis and in future drug development","volume":"64","author":"Bhatt","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1128\/JB.00254-07","article-title":"The two carboxylases of Corynebacterium glutamicum essential for fatty acid and mycolic acid synthesis","volume":"189","author":"Gande","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bibens, L., Becker, J.-P., Dassonville-Klimpt, A., and Sonnet, P. (2023). A review of fatty acid biosynthesis enzyme inhibitors as promising antimicrobial drugs. Pharmaceuticals, 16.","DOI":"10.3390\/ph16030425"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1099\/00221287-147-7-1825","article-title":"Separation and characterization of individual mycolic acids in representative mycobacteria","volume":"147","author":"Watanabe","year":"2001","journal-title":"Microbiology"},{"key":"ref_42","first-page":"1949","article-title":"Isolation of arabinose phosphate from the walls of Mycobacterium tuberculosis H 37 Ra","volume":"277","author":"Amar","year":"1973","journal-title":"Comptes Rendus Hebd. Seances L\u2019academie Sci. Ser. D Sci. Nat."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7820","DOI":"10.1074\/jbc.271.13.7820","article-title":"Biosynthesis of the Linkage Region of the Mycobacterial Cell Wall (\u2217)","volume":"271","author":"Mikus","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1574-6968.2010.02045.x","article-title":"Mycobacterium tuberculosis Rv1302 and Mycobacterium smegmatis MSMEG_4947 have WecA function and MSMEG_4947 is required for the growth of M. smegmatis","volume":"310","author":"Jin","year":"2010","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"43540","DOI":"10.1074\/jbc.M407782200","article-title":"Inactivation of the mycobacterial rhamnosyltransferase, which is needed for the formation of the arabinogalactan-peptidoglycan linker, leads to irreversible loss of viability","volume":"279","author":"Mills","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.1099\/mic.0.2008\/023366-0","article-title":"Development of a microtitre plate-based assay for lipid-linked glycosyltransferase products using the mycobacterial cell wall rhamnosyltransferase WbbL","volume":"154","author":"Grzegorzewicz","year":"2008","journal-title":"Microbiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.bbrc.2006.01.130","article-title":"rmlB and rmlC genes are essential for growth of mycobacteria","volume":"342","author":"Li","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1128\/JB.184.12.3392-3395.2002","article-title":"Formation of dTDP-rhamnose is essential for growth of mycobacteria","volume":"184","author":"Ma","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Konyarikov\u00e1, Z., Savkov\u00e1, K., Kozmon, S., and Miku\u0161ov\u00e1, K. (2020). Biosynthesis of galactan in Mycobacterium tuberculosis as a viable TB drug target?. Antibiotics, 9.","DOI":"10.3390\/antibiotics9010020"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1128\/JB.01326-07","article-title":"Galactosyl transferases in mycobacterial cell wall synthesis","volume":"190","author":"Brennan","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e2023663118","DOI":"10.1073\/pnas.2023663118","article-title":"An ABC transporter Wzm\u2013Wzt catalyzes translocation of lipid-linked galactan across the plasma membrane in mycobacteria","volume":"118","author":"Kozmon","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32362","DOI":"10.1074\/jbc.M506339200","article-title":"Deletion of Cg-emb in corynebacterianeae leads to a novel truncated cell wall arabinogalactan, whereas inactivation of Cg-ubiA results in an arabinan-deficient mutant with a cell wall galactan core","volume":"280","author":"Alderwick","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"15653","DOI":"10.1074\/jbc.M600045200","article-title":"Identification of a novel arabinofuranosyltransferase (AftA) involved in cell wall arabinan biosynthesis in Mycobacterium tuberculosis","volume":"281","author":"Alderwick","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"48854","DOI":"10.1074\/jbc.M102272200","article-title":"The role of the embA and embB gene products in the biosynthesis of the terminal hexaarabinofuranosyl motif of Mycobacterium smegmatisarabinogalactan","volume":"276","author":"Escuyer","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1126\/science.aba9102","article-title":"Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol","volume":"368","author":"Zhang","year":"2020","journal-title":"Science"},{"key":"ref_56","first-page":"398","article-title":"PA-94, an antibiotic identical with D-4-amino-3-isoxazolidinone (cycloserine, oxamycin)","volume":"5","author":"Shull","year":"1955","journal-title":"Antibiot. Chemother. (Northfield)"},{"key":"ref_57","unstructured":"Harned, R.L., Hidy, P., and La Baw, E.K. (1955). Cycloserine. 1. A Preliminary Report. Antibiot. Chemother., 5."},{"key":"ref_58","first-page":"386","article-title":"The isolation of an antibiotic produced by a strain of streptomyces K-300","volume":"3","author":"Kurosawa","year":"1952","journal-title":"Yokohama Med. Bull."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1038\/s41589-020-0498-9","article-title":"D-Cycloserine destruction by alanine racemase and the limit of irreversible inhibition","volume":"16","author":"Prosser","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1021\/ja972907b","article-title":"An aromatization mechanism of inactivation of \u03b3-aminobutyric acid aminotransferase for the antibiotic L-cycloserine","volume":"120","author":"Olson","year":"1998","journal-title":"J. Am. Chem. Soc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1021\/ja973353f","article-title":"D-cycloserine inactivation of D-amino acid aminotransferase leads to a stable noncovalent protein complex with an aromatic cycloserine-PLP derivative","volume":"120","author":"Peisach","year":"1998","journal-title":"J. Am. Chem. Soc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3109\/14756366.2015.1050010","article-title":"Inhibitors of alanine racemase enzyme: A review","volume":"31","author":"Azam","year":"2016","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1021\/ml400349n","article-title":"Metabolomics reveal d-alanine: D-alanine ligase as the target of d-cycloserine in Mycobacterium tuberculosis","volume":"4","author":"Prosser","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1017\/S1461145712000910","article-title":"A randomized add-on trial of high-dose D-cycloserine for treatment-resistant depression","volume":"16","author":"Gelfin","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_65","unstructured":"Neu, H.C., and Gootz, T.D. (1996). Antimicrobial chemotherapy. Medical Microbiology, University of Texas Medical Branch. [4th ed.]."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1111\/febs.12108","article-title":"Kinetic mechanism and inhibition of Mycobacterium tuberculosis D-alanine: D-alanine ligase by the antibiotic D-cycloserine","volume":"280","author":"Prosser","year":"2013","journal-title":"FEBS J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.mib.2019.10.008","article-title":"Antibiotics: Past, present and future","volume":"51","author":"Hutchings","year":"2019","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"763","DOI":"10.2147\/IDR.S194484","article-title":"Efficacy and safety of cycloserine-containing regimens in the treatment of multidrug-resistant tuberculosis: A nationwide retrospective cohort study in China","volume":"12","author":"Wang","year":"2019","journal-title":"Infect. Drug Resist."},{"key":"ref_69","first-page":"35","article-title":"Psychosis associated with cycloserine","volume":"93","author":"Bankier","year":"1965","journal-title":"Can. Med. Assoc. J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/0028-3908(91)90161-4","article-title":"Actions of D-cycloserine at the N-methyl-D-aspartate-associated glycine receptor site in vivo","volume":"30","author":"Emmett","year":"1991","journal-title":"Neuropharmacology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1523\/JNEUROSCI.5390-09.2010","article-title":"Structural determinants of D-cycloserine efficacy at the NR1\/NR2C NMDA receptors","volume":"30","author":"Dravid","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S0028-3908(01)00073-9","article-title":"Subunit specificity and mechanism of action of NMDA partial agonist D-cycloserine","volume":"41","author":"Sheinin","year":"2001","journal-title":"Neuropharmacology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1021\/acsbiomedchemau.2c00074","article-title":"Structure of the D-cycloserine-resistant variant D322N of alanine racemase from Mycobacterium tuberculosis","volume":"3","author":"Prosser","year":"2023","journal-title":"ACS Bio Med Chem Au"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/ng.3548","article-title":"Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance","volume":"48","author":"Desjardins","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_75","first-page":"181","article-title":"Threats to validity in retrospective studies","volume":"3","author":"Tofthagen","year":"2012","journal-title":"J. Adv. Pract. Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5806","DOI":"10.1128\/AAC.00456-20","article-title":"Acetylation of isoniazid is a novel mechanism of isoniazid resistance in Mycobacterium tuberculosis","volume":"65","author":"Arun","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_77","first-page":"400","article-title":"Hydrazine derivatives of pyridinecarboxylic acids","volume":"33","author":"Meller","year":"1912","journal-title":"Monatsschr. Psychiatr. Neurol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1128\/AAC.27.3.399","article-title":"Peroxidase-mediated oxidation of isoniazid","volume":"27","author":"Shoeb","year":"1985","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.meegid.2016.09.004","article-title":"Overview on mechanisms of isoniazid action and resistance in Mycobacterium tuberculosis","volume":"45","author":"Unissa","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1111\/j.1365-2958.2006.05467.x","article-title":"Mechanisms of action of isoniazid","volume":"62","author":"Timmins","year":"2006","journal-title":"Mol. Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1099\/00221287-146-2-289","article-title":"InhA, a target of the antituberculous drug isoniazid, is involved in a mycobacterial fatty acid elongation system, FAS-II","volume":"146","author":"Marrakchi","year":"2000","journal-title":"Microbiology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"8990","DOI":"10.1021\/bi002614m","article-title":"Evidence for isoniazid-dependent free radical generation catalyzed by Mycobacterium tuberculosi s KatG and the isoniazid-resistant mutant KatG (S315T)","volume":"40","author":"Wengenack","year":"2001","journal-title":"Biochemistry"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"102100","DOI":"10.1016\/j.tube.2021.102100","article-title":"Reinvestigation of the structure-activity relationships of isoniazid","volume":"129","author":"Hegde","year":"2021","journal-title":"Tuberculosis"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3987\/REV-88-SR1","article-title":"Recent developments of free-radical substitutions of heteroaromatic bases","volume":"28","author":"Minisci","year":"1989","journal-title":"Heterocycles"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1023\/A:1008741731244","article-title":"The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples","volume":"19","author":"Testa","year":"2000","journal-title":"Perspect. Drug Discov. Des."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Whitney, J.B., and Wainberg, M.A. (2002). Isoniazid, the frontline of resistance in Mycobacterium tuberculosis. McGill J. Med., 6.","DOI":"10.26443\/mjm.v6i2.686"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1128\/AAC.39.11.2472","article-title":"Characterization of the katG and inhA genes of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis","volume":"39","author":"Rouse","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ijmyco.2014.08.003","article-title":"Computational approach to understanding the mechanism of action of isoniazid, an anti-TB drug","volume":"3","author":"Jena","year":"2014","journal-title":"Int. J. Mycobacteriol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0891-5849(96)00277-8","article-title":"Hydrogen bond formation as basis for radical scavenging activity: A structure\u2013activity study of C-methylated dihydrochalcones from Myrica gale and structurally related acetophenones","volume":"22","author":"Mathiesen","year":"1997","journal-title":"Free Radic. Biol. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1128\/AAC.46.7.2137-2144.2002","article-title":"Mn (III) pyrophosphate as an efficient tool for studying the mode of action of isoniazid on the InhA protein of Mycobacterium tuberculosis","volume":"46","author":"Nguyen","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1084\/jem.20062100","article-title":"Mechanism of thioamide drug action against tuberculosis and leprosy","volume":"204","author":"Wang","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_92","first-page":"527","article-title":"Identification, characterization and synthesis of potential related substances of ethionamide","volume":"8","author":"Sawant","year":"2015","journal-title":"Ras. J. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"12824","DOI":"10.1074\/jbc.M110751200","article-title":"The antituberculosis drug ethionamide is activated by a flavoprotein monooxygenase\u2217","volume":"277","author":"Vannelli","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1007\/s11094-022-02782-0","article-title":"Ethionamide and Prothionamide Based Coumarinyl-Thiazole Derivatives: Synthesis, Antitubercular Activity, Toxicity Investigations and Molecular Docking Studies","volume":"56","author":"Imran","year":"2022","journal-title":"Pharm. Chem. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"511","DOI":"10.2174\/1386207322666190722162100","article-title":"Synthesis, in silico and biological studies of thiazolyl-2h-chromen-2-one derivatives as potent antitubercular agents","volume":"16","author":"Jadhav","year":"2020","journal-title":"Curr. Comput.-Aided Drug Des."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3788","DOI":"10.1016\/j.ejmech.2011.05.044","article-title":"Synthesis and antimicrobial properties of some new thiazolyl coumarin derivatives","volume":"46","author":"Arshad","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"9677","DOI":"10.1073\/pnas.97.17.9677","article-title":"Ethionamide activation and sensitivity in multidrug-resistant Mycobacterium tuberculosis","volume":"97","author":"DeBarber","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1128\/AAC.36.6.1316","article-title":"Mycolic acid synthesis: A target for ethionamide in mycobacteria?","volume":"36","author":"Lacave","year":"1992","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2174\/138920013804545151","article-title":"Metabolism of the antituberculosis drug ethionamide","volume":"14","author":"Vale","year":"2013","journal-title":"Curr. Drug Metab."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1007\/s00228-001-0396-3","article-title":"Isoniazid is a mechanism-based inhibitor of cytochrome P 450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes","volume":"57","author":"Wen","year":"2002","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"837","DOI":"10.7326\/0003-4819-100-6-837","article-title":"Ethionamide-lnduced goitrous hypothyroidism","volume":"100","author":"Drucker","year":"1984","journal-title":"Ann. Intern. Med."},{"key":"ref_102","first-page":"161","article-title":"Ethionamide-induced hypothyroidism in children","volume":"26","author":"Hallbauer","year":"2011","journal-title":"S. Afr. J. Epidemiol. Infect."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1001\/jama.1981.03320100038026","article-title":"Single high-dose pyridoxine treatment for isoniazid overdose","volume":"246","author":"Wason","year":"1981","journal-title":"Jama"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1001\/jama.1958.63000030004011a","article-title":"Use of pyridoxine hydrochloride to prevent isoniazid toxicity","volume":"168","author":"Ross","year":"1958","journal-title":"J. Am. Med. Assoc."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"68","DOI":"10.2471\/BLT.13.122028","article-title":"Principles for designing future regimens for multidrug-resistant tuberculosis","volume":"92","author":"Brigden","year":"2013","journal-title":"Bull. World Health Organ."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.tube.2018.04.008","article-title":"Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB)","volume":"111","author":"Liu","year":"2018","journal-title":"Tuberculosis"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"106041","DOI":"10.1016\/j.jddst.2024.106041","article-title":"Delamanid proliposomal powder aerosols targeting alveolar macrophages for treatment of pulmonary extensively drug-resistant tuberculosis treatment: Bioactivity, biocompatibility, and structure elucidation","volume":"100","author":"Tongkanarak","year":"2024","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.1021\/jm501608q","article-title":"Synthesis and structure\u2013activity relationships for extended side chain analogues of the antitubercular drug (6 S)-2-nitro-6-{[4-(trifluoromethoxy) benzyl] oxy}-6, 7-dihydro-5 H-imidazo [2, 1-b][1, 3] oxazine (PA-824)","volume":"58","author":"Palmer","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Matsumoto, M., Hashizume, H., Tomishige, T., Kawasaki, M., Tsubouchi, H., Sasaki, H., Shimokawa, Y., and Komatsu, M. (2006). OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030466"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wermuth, C.G. (2008). Designing prodrugs and bioprecursors. The Practice of Medicinal Chemistry, Elsevier.","DOI":"10.1016\/B978-0-12-374194-3.00036-6"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1742-4658.2011.08404.x","article-title":"Substrate specificity of the deazaflavin-dependent nitroreductase from Mycobacterium tuberculosis responsible for the bioreductive activation of bicyclic nitroimidazoles","volume":"279","author":"Gurumurthy","year":"2012","journal-title":"FEBS J."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/35016103","article-title":"A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis","volume":"405","author":"Stover","year":"2000","journal-title":"Nature"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.1038\/s41467-023-39300-z","article-title":"DprE2 is a molecular target of the anti-tubercular nitroimidazole compounds pretomanid and delamanid","volume":"14","author":"Abrahams","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1111\/j.1742-4658.2008.06395.x","article-title":"Biosynthesis of D-arabinose in mycobacteria\u2013a novel bacterial pathway with implications for antimycobacterial therapy","volume":"275","author":"Wolucka","year":"2008","journal-title":"FEBS J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"8020","DOI":"10.1128\/JB.187.23.8020-8025.2005","article-title":"Decaprenylphosphoryl arabinofuranose, the donor of the D-arabinofuranosyl residues of mycobacterial arabinan, is formed via a two-step epimerization of decaprenylphosphoryl ribose","volume":"187","author":"Huang","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.tube.2017.12.006","article-title":"Mechanisms of resistance to delamanid, a drug for Mycobacterium tuberculosis","volume":"108","author":"Fujiwara","year":"2018","journal-title":"Tuberculosis"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1248\/bpb.b14-00311","article-title":"Delamanid does not inhibit or induce cytochrome p450 enzymes in vitro","volume":"37","author":"Shimokawa","year":"2014","journal-title":"Biol. Pharm. Bull."},{"key":"ref_118","first-page":"779","article-title":"The role of delamanid in the treatment of drug-resistant tuberculosis","volume":"11","author":"Lewis","year":"2015","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1093\/cid\/ciac019","article-title":"Safety of treatment regimens containing bedaquiline and delamanid in the endTB cohort","volume":"75","author":"Hewison","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_120","first-page":"1382","article-title":"Adverse events in the treatment of multidrug-resistant tuberculosis: Results from the DOTS-Plus initiative","volume":"8","author":"Nathanson","year":"2004","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e02144-21","DOI":"10.1128\/aac.02144-21","article-title":"Delamanid added to an optimized background regimen in children with multidrug-resistant tuberculosis: Results of a phase I\/II clinical trial","volume":"66","author":"Frias","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"499","DOI":"10.2174\/156802607780059727","article-title":"Screening for novel antituberculosis agents that are effective against multidrug resistant tuberculosis","volume":"7","author":"Matsumoto","year":"2007","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/bdd.2064","article-title":"Absorption, distribution and excretion of the anti-tuberculosis drug delamanid in rats: Extensive tissue distribution suggests potential therapeutic value for extrapulmonary tuberculosis","volume":"38","author":"Shibata","year":"2017","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1021\/ja01470a052","article-title":"Stereospecificity in a new type of synthetic antituberculous agent1, 2","volume":"83","author":"Wilkinson","year":"1961","journal-title":"J. Am. Chem. Soc."},{"key":"ref_125","first-page":"891","article-title":"A new synthetic compound with antituberculous activity in mice: Ethambutol (dextro-2, 2\u2032-(ethylenediimino)-di-1-butanol)","volume":"83","author":"Thomas","year":"1961","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_126","first-page":"902","article-title":"Therapeutic effect of ethambutol (dextro-2, 2\u2032-[ethylenediimino]-di-l-butanol) on experimental tuberculosis in guinea pigs","volume":"84","author":"Karlson","year":"1961","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_127","first-page":"428","article-title":"A four-year clinical investigation of ethambutol in initial and re-treatment cases of tuberculosis: Efficacy, toxicity, and bacterial resistance","volume":"93","author":"Pyle","year":"1966","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/nm0597-567","article-title":"The emb operon, a gene cluster of Mycobacterium tuberculosis involved in resistance to ethambutol","volume":"3","author":"Telenti","year":"1997","journal-title":"Nat. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2174\/138945008783502449","article-title":"Molecular mechanisms of host-pathogen interactions and their potential for the discovery of new drug targets","volume":"9","author":"Briken","year":"2008","journal-title":"Curr. Drug Targets"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1084\/jem.20051239","article-title":"The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis","volume":"202","author":"Kang","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1038\/24206","article-title":"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence","volume":"396","author":"Cole","year":"1998","journal-title":"Nature"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"4138","DOI":"10.1128\/AAC.00162-09","article-title":"The arabinosyltransferase EmbC is inhibited by ethambutol in Mycobacterium tuberculosis","volume":"53","author":"Goude","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1093\/jac\/dkq120","article-title":"embCAB sequence variation among ethambutol-resistant Mycobacterium tuberculosis isolates without embB 306 mutation","volume":"65","author":"Plinke","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Xu, Y., Jia, H., Huang, H., Sun, Z., and Zhang, Z. (2015). Mutations found in embCAB, embR, and ubiA genes of ethambutol-sensitive and-resistant Mycobacterium tuberculosis clinical isolates from China. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/951706"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/j.1749-6632.1966.tb45526.x","article-title":"Ethambutol in the retreatment and primary treatment of tuberculosis: A four-year clinical investigation","volume":"135","author":"Pyle","year":"1966","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1111\/j.1749-6632.1966.tb45532.x","article-title":"The ocular toxicity of ethambutol and its relation to dose","volume":"135","author":"Leibold","year":"1966","journal-title":"Ann. N. Y.Acad. Sci."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"451","DOI":"10.2174\/138955707780619617","article-title":"Chirality-A new era of therapeutics","volume":"7","author":"Agrawal","year":"2007","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_138","unstructured":"World Health Organization (1991). WHO Model Prescribing Information: Drugs Used in Mycobacterial Diseases, World Health Organization."},{"key":"ref_139","first-page":"190","article-title":"Ethambutol is toxic to retinal ganglion cells via an excitotoxic pathway","volume":"40","author":"Heng","year":"1999","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.aanat.2015.11.006","article-title":"Effect of memantine: A NMDA receptor blocker, on ethambutol-induced retinal injury","volume":"204","author":"Firgany","year":"2016","journal-title":"Ann. Anat.-Anat. Anz."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"447","DOI":"10.5588\/ijtld.11.0766","article-title":"Incidence of ethambutol-related visual impairment during treatment of active tuberculosis","volume":"17","author":"Ezer","year":"2013","journal-title":"Int. J. Tuberc. Lung Dis."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1097\/WNO.0b013e3182901969","article-title":"Drug-related mitochondrial optic neuropathies","volume":"33","author":"Wang","year":"2013","journal-title":"J. Neuro-Ophthalmol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Wallis, R.S., Dawson, R., Friedrich, S.O., Venter, A., Paige, D., Zhu, T., Silvia, A., Gobey, J., Ellery, C., and Zhang, Y. (2014). Mycobactericidal activity of sutezolid (PNU-100480) in sputum (EBA) and blood (WBA) of patients with pulmonary tuberculosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094462"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.4155\/fmc.15.128","article-title":"The anti-tuberculosis agents under development and the challenges ahead","volume":"7","author":"Kumar","year":"2015","journal-title":"Future Med. Chem."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Hariguchi, N., Chen, X., Hayashi, Y., Kawano, Y., Fujiwara, M., Matsuba, M., Shimizu, H., Ohba, Y., Nakamura, I., and Kitamoto, R. (2020). OPC-167832, a novel carbostyril derivative with potent antituberculosis activity as a DprE1 inhibitor. Antimicrob. Agents Chemother., 64.","DOI":"10.1128\/AAC.02020-19"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.drudis.2016.09.014","article-title":"Structural studies of Mycobacterium tuberculosis DprE1 interacting with its inhibitors","volume":"22","author":"Piton","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_147","unstructured":"Xue, B., Okusanya, O., and Zhu, T. (2012, January 9\u201312). Pharmacokinetic-pharmacodynamic (PK-PD) analysis evaluating the effects of rifampin (RIF), PNU-100480 (sutezolid, U-480), and its metabolite PNU-101603 (U-603), alone and in combination, against Mycobacterium tuberculosis (Mtb) in the nonreplicating persister (NRP) state using data from a hollow-fiber infection model (HFIM). Proceedings of the 52nd Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC), San Francisco, CA, USA."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1128\/AAC.01182-08","article-title":"Promising antituberculosis activity of the oxazolidinone PNU-100480 relative to that of linezolid in a murine model","volume":"53","author":"Williams","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1164\/rccm.200904-0611OC","article-title":"Addition of PNU-100480 to first-line drugs shortens the time needed to cure murine tuberculosis","volume":"180","author":"Williams","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1128\/AAC.01920-13","article-title":"Population pharmacokinetic\/pharmacodynamic analysis of the bactericidal activities of sutezolid (PNU-100480) and its major metabolite against intracellular Mycobacterium tuberculosis in ex vivo whole-blood cultures of patients with pulmonary tuberculosis","volume":"58","author":"Zhu","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Makarov, V., and Miku\u0161ov\u00e1, K. (2020). Development of macozinone for TB treatment: An update. Appl. Sci., 10.","DOI":"10.3390\/app10072269"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"5728","DOI":"10.1021\/jm500571f","article-title":"Lead optimization of 1, 4-azaindoles as antimycobacterial agents","volume":"57","author":"Shirude","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1021\/acsmedchemlett.9b00343","article-title":"Scaffold morphing to identify novel DprE1 inhibitors with antimycobacterial activity","volume":"10","author":"Shandil","year":"2019","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4697","DOI":"10.1039\/D3CC00356F","article-title":"Synthesis, structures, reactivity and medicinal chemistry of antitubercular benzothiazinones","volume":"59","author":"Seidel","year":"2023","journal-title":"Chem. Commun."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1080\/08927022.2019.1659507","article-title":"Decoding the signature of molecular mechanism involved in mutation associated resistance to 1, 3-benzothiazin-4-ones (Btzs) based DprE1 inhibitors using BTZ043 as a reference drug","volume":"45","author":"Verma","year":"2019","journal-title":"Mol. Simul."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1093\/jac\/dkl095","article-title":"Synthesis and antileprosy activity of some dialkyldithiocarbamate","volume":"57","author":"Marakov","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/nchembio.794","article-title":"Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane","volume":"8","author":"Grzegorzewicz","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Degiacomi, G., Benjak, A., Madacki, J., Boldrin, F., Provvedi, R., Pal\u00f9, G., Kordulakova, J., Cole, S.T., and Manganelli, R. (2017). Essentiality of mmpL3 and impact of its silencing on Mycobacterium tuberculosis gene expression. Sci. Rep., 7.","DOI":"10.1038\/srep43495"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"6121","DOI":"10.1073\/pnas.1030024100","article-title":"MmpL8 is required for sulfolipid-1 biosynthesis and Mycobacterium tuberculosis virulence","volume":"100","author":"Converse","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"24213","DOI":"10.1074\/jbc.M113.473371","article-title":"MmpL11 protein transports mycolic acid-containing lipids to the mycobacterial cell wall and contributes to biofilm formation in Mycobacterium smegmatis","volume":"288","author":"Pacheco","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.chembiol.2012.03.006","article-title":"MmpL genes are associated with mycolic acid metabolism in mycobacteria and corynebacteria","volume":"19","author":"Varela","year":"2012","journal-title":"Chem. Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.2174\/1389557516666160118105319","article-title":"MmpL3 inhibitors: Diverse chemical scaffolds inhibit the same target","volume":"16","author":"Poce","year":"2016","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1128\/AAC.05270-11","article-title":"MmpL3 is the cellular target of the antitubercular pyrrole derivative BM212","volume":"56","author":"Poce","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Remui\u00f1\u00e1n, M.J., P\u00e9rez-Herr\u00e1n, E., Rull\u00e1s, J., Alemparte, C., Mart\u00ednez-Hoyos, M., Dow, D.J., Afari, J., Mehta, N., Esquivias, J., and Jim\u00e9nez, E. (2013). Tetrahydropyrazolo [1, 5-a] pyrimidine-3-carboxamide and N-benzyl-6\u2032, 7\u2032-dihydrospiro [piperidine-4, 4\u2032-thieno [3, 2-c] pyran] analogues with bactericidal efficacy against Mycobacterium tuberculosis targeting MmpL3. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060933"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1021\/acsinfecdis.6b00052","article-title":"Diphenylether-modified 1, 2-diamines with improved drug properties for development against Mycobacterium tuberculosis","volume":"2","author":"Foss","year":"2016","journal-title":"ACS Infect. Dis."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"6413","DOI":"10.1128\/AAC.03229-14","article-title":"Novel insights into the mechanism of inhibition of MmpL3, a target of multiple pharmacophores in Mycobacterium tuberculosis","volume":"58","author":"Li","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Williams, J.T., Haiderer, E.R., Coulson, G.B., Conner, K.N., Ellsworth, E., Chen, C., Alvarez-Cabrera, N., Li, W., Jackson, M., and Dick, T. (2019). Identification of new MmpL3 inhibitors by untargeted and targeted mutant screens defines MmpL3 domains with differential resistance. Antimicrob. Agents Chemother., 63.","DOI":"10.1128\/AAC.00547-19"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1021\/cb300151m","article-title":"Identification of novel inhibitors of M. tuberculosis growth using whole cell based high-throughput screening","volume":"7","author":"Stanley","year":"2012","journal-title":"ACS Chem. Biol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1002\/cmdc.202100359","article-title":"Mycobacterial membrane protein large 3 (MmpL3) inhibitors: A promising approach to combat tuberculosis","volume":"16","author":"Umare","year":"2021","journal-title":"ChemMedChem"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"6","DOI":"10.21292\/2075-1230-2018-96-3-6-18","article-title":"Efficiency and safety of chemotherapy regimen with SQ109 in those suffering from multiple drug resistant tuberculosis","volume":"96","author":"Borisov","year":"2018","journal-title":"Tuberc. Lung Dis."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1124\/jpet.105.087817","article-title":"Pharmacoproteomic effects of isoniazid, ethambutol, and N-geranyl-N\u2032-(2-adamantyl) ethane-1, 2-diamine (SQ109) on Mycobacterium tuberculosis H37Rv","volume":"315","author":"Jia","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"5356","DOI":"10.1021\/acs.jcim.3c00616","article-title":"Inhibition Mechanism of Anti-TB Drug SQ109: Allosteric Inhibition of TMM Translocation of Mycobacterium tuberculosis MmpL3 Transporter","volume":"63","author":"Carbone","year":"2023","journal-title":"J. Chem. Inf. Model."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/1\/70\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:25:41Z","timestamp":1759919141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/1\/70"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":172,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ph18010070"],"URL":"https:\/\/doi.org\/10.3390\/ph18010070","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]}}}