{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:16:24Z","timestamp":1788232584341,"version":"build-2803163510"},"reference-count":82,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T00:00:00Z","timestamp":1496275200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/09502-7"],"award-info":[{"award-number":["2016\/09502-7"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Tuberculosis (TB), a disease caused mainly by the Mycobacterium tuberculosis (Mtb), is according to the World Health Organization (WHO) the infectious disease responsible for the highest number of deaths worldwide. The increased number of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains, and the ineffectiveness of the current treatment against latent tuberculosis are challenges to be overcome in the coming years. The scenario of drug discovery becomes alarming when it is considered that the number of new drugs does not increase proportionally to the emergence of drug resistance. In this review, we will demonstrate the current advances in antitubercular drug discovery, focusing on the research of compounds with potent antituberculosis activity against MDR-TB strains. Herein, active compounds against MDR-TB with minimum inhibitory concentrations (MICs) less than 11 \u00b5M and low toxicity published in the last 4 years in the databases PubMed, Web of Science and Scopus will be presented and discussed.<\/jats:p>","DOI":"10.3390\/ph10020051","type":"journal-article","created":{"date-parts":[[2017,6,1]],"date-time":"2017-06-01T10:36:36Z","timestamp":1496313396000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Advances in Drug Discovery of New Antitubercular Multidrug-Resistant Compounds"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7644-5466","authenticated-orcid":false,"given":"Guilherme","family":"Fernandes","sequence":"first","affiliation":[{"name":"Institute of Chemistry, S\u00e3o Paulo State University (UNESP), Araraquara 14800060, Brazil"},{"name":"School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung","family":"Man Chin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Dos Santos","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, S\u00e3o Paulo State University (UNESP), Araraquara 14800060, Brazil"},{"name":"School of Pharmaceutical Sciences, S\u00e3o Paulo State University (UNESP), Araraquara 14800903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,1]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2015). Global Tuberculosis Report, World Health Organization."},{"key":"ref_2","unstructured":"World Health Organization (2014). Global Tuberculosis Report 2014 (WHO\/HTM\/TB\/2014.08), World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/nrd4001","article-title":"Advances in the development of new tuberculosis drugs and treatment regimens","volume":"12","author":"Zumla","year":"2013","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3201\/eid1903.120246","article-title":"Emergence and spread of extensively and totally drug-resistant tuberculosis, South Africa","volume":"19","author":"Klopper","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1001\/jama.2013.1802","article-title":"South Africa Warns of Emergence of \u201cTotally\u201d Drug-Resistant Tuberculosis","volume":"309","author":"Slomski","year":"2013","journal-title":"J. Am. Med. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature09657","article-title":"The challenge of new drug discovery for tuberculosis","volume":"469","author":"Koul","year":"2011","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.2174\/0929867322666150818103836","article-title":"Current Advances in Antitubercular Drug Discovery: Potent Prototypes and New Targets","volume":"22","author":"Fernandes","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_8","first-page":"1","article-title":"Tuberculosis","volume":"2","author":"Pai","year":"2016","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1016\/S1473-3099(16)00070-0","article-title":"Tuberculosis\u2014Advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers","volume":"16","author":"Wallis","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1056\/NEJMc1505196","article-title":"Acquired Resistance to Bedaquiline and Delamanid in Therapy for Tuberculosis","volume":"373","author":"Bloemberg","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2542","DOI":"10.1128\/AAC.02941-15","article-title":"Mycobacterium tuberculosis Mutations Associated with Reduced Susceptibility to Linezolid","volume":"60","author":"Zhang","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1128\/AAC.06154-11","article-title":"New mutations in the mycobacterial ATP synthase: New insights into the binding of the diarylquinoline TMC207 to the ATP synthase C-Ring structure","volume":"56","author":"Segala","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1021\/acs.jmedchem.5b00608","article-title":"Development of 3,5-Dinitrobenzylsulfanyl-1,3,4-oxadiazoles and Thiadiazoles as Selective Antitubercular Agents Active Against Replicating and Nonreplicating Mycobacterium tuberculosis","volume":"59","author":"Karabanovich","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ejmech.2016.11.041","article-title":"S-substituted 3,5-dinitrophenyl 1,3,4-oxadiazole-2-thiols and tetrazole-5-thiols as highly efficient antitubercular agents","volume":"126","author":"Karabanovich","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/S1471-4892(01)00082-0","article-title":"Oxazolidinones: A new class of antibacterials","volume":"1","author":"Zurenko","year":"2001","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13339","DOI":"10.1073\/pnas.0804276105","article-title":"The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning","volume":"105","author":"Wilson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1128\/AAC.01903-13","article-title":"Bactericidal activity and mechanism of action of AZD5847, a novel oxazolidinone for treatment of tuberculosis","volume":"58","author":"Balasubramanian","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6591","DOI":"10.1128\/AAC.01163-16","article-title":"Early Bactericidal Activity of AZD5847 in Patients with Pulmonary Tuberculosis","volume":"60","author":"Furin","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1016\/j.bmcl.2014.02.025","article-title":"Discovery of novel bis-oxazolidinone compounds as potential potent and selective antitubercular agents","volume":"24","author":"Ang","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ejmech.2014.10.031","article-title":"Synthesis and evaluation of in vitro antimycobacterial activity of novel 1H-benzo[d]imidazole derivatives and analogues","volume":"89","author":"Gobis","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1016\/j.bmc.2015.03.008","article-title":"Novel 2-(2-phenalkyl)-1H-benzo[d]imidazoles as antitubercular agents. Synthesis, biological evaluation and structure-activity relationship","volume":"23","author":"Gobis","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3118","DOI":"10.1016\/j.bmcl.2014.05.006","article-title":"Synthesis and antituberculosis activity of novel 5-styryl-4-(hetero)aryl- pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and S NH reactions","volume":"24","author":"Kravchenko","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1016\/j.bmc.2016.06.020","article-title":"Synthesis and evaluation of antitubercular activity of fluorinated 5-aryl-4-(hetero)aryl substituted pyrimidines","volume":"24","author":"Verbitskiy","year":"2016","journal-title":"Bioorg. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6837","DOI":"10.1016\/j.bmc.2014.10.035","article-title":"Antitubercular activity of quinolizidinyl\/pyrrolizidinylalkyliminophenazines","volume":"22","author":"Tonelli","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5325","DOI":"10.1128\/AAC.03233-14","article-title":"1,4-azaindole, A potential drug candidate for treatment of tuberculosis","volume":"58","author":"Chatterji","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9701","DOI":"10.1021\/jm401382v","article-title":"Azaindoles: Noncovalent DprE1 Inhibitors from Scaffold Morphing Efforts, Kill Mycobacterium tuberculosis and Are Efficacious in Vivo","volume":"56","author":"Shirude","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.bmcl.2015.12.049","article-title":"Synthesis and antituberculosis activity of indole-pyridine derived hydrazides, hydrazide-hydrazones, and thiosemicarbazones","volume":"26","author":"Velezheva","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.ejmech.2013.09.061","article-title":"Antimycobacterial activity of nitrogen heterocycles derivatives: Bipyridine derivatives. Part III","volume":"74","author":"Danac","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4761","DOI":"10.1021\/jm5002937","article-title":"Discovery of pyrazolopyridones as a novel class of noncovalent DprE1 inhibitor with potent anti-mycobacterial activity","volume":"57","author":"Panda","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"8841","DOI":"10.1007\/s00253-013-5218-x","article-title":"The DprE1 enzyme, one of the most vulnerable targets of Mycobacterium tuberculosis","volume":"97","author":"Riccardi","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1021\/acschembio.5b00237","article-title":"DprE1 Is a Vulnerable Tuberculosis Drug Target Due to Its Cell Wall Localization","volume":"10","author":"Brecik","year":"2015","journal-title":"ACS Chem. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1021\/acsmedchemlett.5b00176","article-title":"Design, Synthesis, and Biological Evaluation of Pyrazolo[1,5-a]pyridine-3-carboxamides as Novel Antitubercular Agents","volume":"6","author":"Tang","year":"2015","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1021\/acsmedchemlett.6b00330","article-title":"Identification of N -(2-Phenoxyethyl)imidazo[1,2-a]pyridine-3-carboxamides as New Antituberculosis Agents","volume":"7","author":"Wu","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1021\/acs.jmedchem.6b00031","article-title":"Design and Synthesis of 1-((1,5-Bis(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl)methyl)-4-methylpiperazine (BM212) and N-Adamantan-2-yl-N\u2032-((E)-3,7-dimethylocta-2,6-dienyl)ethane-1,2-diamine (SQ109) Pyrrole Hybrid Derivatives: Discovery of Potent Antituberc","volume":"59","author":"Bhakta","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"492","DOI":"10.3109\/14756366.2014.930454","article-title":"Quinoline and quinolones: Promising scaffolds for future antimycobacterial agents","volume":"30","author":"Singh","year":"2015","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1021\/acsmedchemlett.5b00324","article-title":"2-(Quinolin-4-yloxy)acetamides Are Active against Drug-Susceptible and Drug-Resistant Mycobacterium tuberculosis Strains","volume":"7","author":"Pissinate","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.ejmech.2016.11.048","article-title":"New insights into the SAR and drug combination synergy of 2-(quinolin-4-yloxy)acetamides against Mycobacterium tuberculosis","volume":"126","author":"Giacobbo","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5419","DOI":"10.1021\/jm5005978","article-title":"4-Aminoquinolone piperidine amides: Noncovalent inhibitors of DprE1 with long residence time and potent antimycobacterial activity","volume":"57","author":"Naik","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.ejmech.2015.03.014","article-title":"Synthesis, crystal structure and biological evaluation of substituted quinazolinone benzoates as novel antituberculosis agents targeting acetohydroxyacid synthase","volume":"94","author":"Lu","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"689","DOI":"10.2174\/1389450116666150416115547","article-title":"Mechanisms of bacterial acetohydroxyacid synthase (AHAS) and specific inhibitors of Mycobacterium tuberculosis AHAS as potential drug candidates against tuberculosis","volume":"16","author":"Gokhale","year":"2015","journal-title":"Curr. Drug Targets"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.4155\/fmc.11.90","article-title":"Nitroimidazoles for the treatment of TB: Past, present and future","volume":"3","author":"Mukherjee","year":"2011","journal-title":"Futur. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6063","DOI":"10.1016\/j.bmc.2012.08.023","article-title":"Antitubercular nitrofuran isoxazolines with improved pharmacokinetic properties","volume":"20","author":"Rakesha","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ejmech.2012.10.047","article-title":"Hybrid furoxanyl N-acylhydrazone derivatives as hits for the development of neglected diseases drug candidates","volume":"59","author":"Rojas","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1016\/j.bmc.2017.02.003","article-title":"New nitrofurans amenable by isocyanide multicomponent chemistry are active against multidrug-resistant and poly-resistant Mycobacterium tuberculosis","volume":"25","author":"Krasavin","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"222","DOI":"10.4103\/0976-500X.136121","article-title":"Delamanid: A new armor in combating drug-resistant tuberculosis","volume":"5","author":"Xavier","year":"2014","journal-title":"J. Pharmacol. Pharmacother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1039\/C5OB00054H","article-title":"Synthesis of new generation triazolyl- and isoxazolyl-containing 6-nitro-2,3-dihydroimidazooxazoles as anti-TB agents: In vitro, structure-activity relationship, pharmacokinetics and in vivo evaluation","volume":"13","author":"Munagala","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.ejmech.2016.07.039","article-title":"Synthesis and biological activity of furoxan derivatives against Mycobacterium tuberculosis","volume":"123","author":"Fernandes","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6828","DOI":"10.1128\/AAC.03644-14","article-title":"Nitrotriazole- and imidazole-based amides and sulfonamides as antitubercular agents","volume":"58","author":"Papadopoulou","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9371","DOI":"10.1021\/acs.jmedchem.5b01542","article-title":"Pyrrolo[3,4-c]pyridine-1,3(2H)-diones: A novel antimycobacterial class targeting mycobacterial respiration","volume":"58","author":"Winks","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6134","DOI":"10.1016\/j.bmc.2014.08.031","article-title":"Development of benzo[d]oxazol-2(3H)-ones derivatives as novel inhibitors of Mycobacterium tuberculosis InhA","volume":"22","author":"Pedgaonkar","year":"2014","journal-title":"Bioorganic Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5178","DOI":"10.1016\/j.bmcl.2015.09.072","article-title":"Discovery of the disubstituted oxazole analogues as a novel class anti-tuberculotic agents against MDR- and XDR-MTB","volume":"25","author":"Li","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.2174\/1568026616666160506131118","article-title":"Sulphur-Containing Heterocycles as Antimycobacterial Agents: Recent Advances in Thiophene and Thiadiazole Derivatives","volume":"16","author":"Vinsova","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6572","DOI":"10.1021\/jm500833f","article-title":"Diarylthiazole: An antimycobacterial scaffold potentially targeting PrrB-PrrA two-component system","volume":"57","author":"Bellale","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1128\/JB.06258-11","article-title":"Transient requirement of the PrrA-PrrB two-component system for early intracellular multiplication of Mycobacterium tuberculosis","volume":"194","author":"Haydel","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1128\/IAI.70.5.2256-2263.2002","article-title":"Transient Requirement of the PrrA-PrrB Two-Component System for Early Intracellular Multiplication of Mycobacterium tuberculosis","volume":"70","author":"Ewann","year":"2002","journal-title":"Infect. Immun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"29717","DOI":"10.1038\/srep29717","article-title":"Benzothiazinethione is a potent preclinical candidate for the treatment of drug-resistant tuberculosis","volume":"6","author":"Gao","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1126\/science.1171583","article-title":"Benzothiazinones kill Mycobacterium tuberculosis by blocking arabinan synthesis","volume":"324","author":"Makarov","year":"2009","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejmech.2013.11.007","article-title":"Design, synthesis and investigation on the structure-activity relationships of N-substituted 2-aminothiazole derivatives as antitubercular agents","volume":"72","author":"Pieroni","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7694","DOI":"10.1016\/j.bmc.2015.11.017","article-title":"Discovery of benzothiazoles as antimycobacterial agents: Synthesis, structure-activity relationships and binding studies with Mycobacterium tuberculosis decaprenylphosphoryl-B-D-ribose 2\u2019-oxidase","volume":"23","author":"Landge","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ejmech.2015.07.039","article-title":"Linked pyridinyl-thiadiazoles: Design and synthesis as potential candidate for treatment of XDR and MDR tuberculosis","volume":"102","author":"Mahajan","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ejmech.2015.05.007","article-title":"Synthesis, and structure-activity relationship for C(4) and\/or C(5) thienyl substituted pyrimidines, as a new family of antimycobacterial compounds","volume":"97","author":"Verbitskiy","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2528","DOI":"10.1002\/cmdc.201402255","article-title":"Biological evaluation of potent triclosan-derived inhibitors of the enoyl-acyl carrier protein reductase InhA in drug-sensitive and drug-resistant strains of Mycobacterium tuberculosis","volume":"9","author":"Stec","year":"2014","journal-title":"ChemMedChem"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6232","DOI":"10.1021\/acs.jmedchem.6b00415","article-title":"Indole-2-carboxamide-based MmpL3 Inhibitors Show Exceptional Antitubercular Activity in an Animal Model of Tuberculosis Infection","volume":"59","author":"Stec","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1016\/j.bmcl.2016.03.059","article-title":"Seeking potent anti-tubercular agents: Design, synthesis, anti-tubercular activity and docking study of various ((triazoles\/indole)-piperazin-1-yl\/1,4-diazepan-1-yl)benzo[d]isoxazole derivatives","volume":"26","author":"Naidu","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1021\/acsmedchemlett.6b00077","article-title":"Synthesis and Antitubercular Activity of New Benzo[b]thiophenes","volume":"7","author":"Mahajan","year":"2016","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.bmcl.2015.01.050","article-title":"A novel molecule with notable activity against multi-drug resistant tuberculosis","volume":"25","author":"Nair","year":"2015","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Lu, X., Hu, X., Liu, Z., Zhang, T., Wang, R., Wan, B., Franzblau, S., and You, Q. (2017). Benzylsulfanyl benzo-heterocycle amides and hydrazones as new agents against drug susceptible and resistant Mycobacterium tuberculosis. Med. Chem. Commun.","DOI":"10.1039\/C7MD00146K"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12904","DOI":"10.1021\/bi011522+","article-title":"Steady-State and Pre-Steady-State Kinetic Analysis of Mycobacterium tuberculosis Pantothenate Synthetase","volume":"40","author":"Zheng","year":"2001","journal-title":"Biochemistry"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/nrd2445","article-title":"The influence of drug-like concepts on decision-making in medicinal chemistry","volume":"6","author":"Leeson","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S1461-5347(98)00097-2","article-title":"Physical chemical properties of oral drug candidates in the discovery and exploratory development settings","volume":"1","author":"Curatolo","year":"1998","journal-title":"Pharm. Sci. Technol. Today"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/nyas.12459","article-title":"Tuberculosis drug discovery and emerging targets","volume":"1323","author":"Mdluli","year":"2014","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1021\/mp300537k","article-title":"In Silico Physicochemical Parameter Predictions","volume":"10","author":"Wenlock","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/S1359-6446(05)03584-1","article-title":"Computing chemistry on the web","volume":"10","author":"Tetko","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and developmental settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_77","unstructured":"(2017, May 29). Organic Chemistry Portal Fragment Based Druglikeness. Available online: http:\/\/www.organic-chemistry.org\/prog\/peo\/druglike."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2217\/fmb.14.125","article-title":"The future for early-stage tuberculosis drug discovery","volume":"10","author":"Zuniga","year":"2015","journal-title":"Futur. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5087","DOI":"10.1016\/j.bmc.2014.12.031","article-title":"Perspective: Challenges and opportunities in TB drug discovery from phenotypic screening","volume":"23","author":"Manjunatha","year":"2015","journal-title":"Bioorg. Med. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1517\/17460441003605098","article-title":"Lipophilicity in drug discovery","volume":"5","author":"Waring","year":"2010","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/hep.26208","article-title":"High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury","volume":"58","author":"Chen","year":"2013","journal-title":"Hepatology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1021\/jm301514n","article-title":"Contributions of molecular properties to drug promiscuity","volume":"56","author":"Tarcsay","year":"2013","journal-title":"J. Med. Chem."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/10\/2\/51\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:37:36Z","timestamp":1760207856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/10\/2\/51"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,1]]},"references-count":82,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,6]]}},"alternative-id":["ph10020051"],"URL":"https:\/\/doi.org\/10.3390\/ph10020051","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,1]]}}}