{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T02:25:19Z","timestamp":1778984719848,"version":"3.51.4"},"reference-count":69,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIH\/NIAID","doi-asserted-by":"publisher","award":["1R15AI142609-01A1"],"award-info":[{"award-number":["1R15AI142609-01A1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Mycobacterium abscessus (MAB) is a highly resilient pathogen that causes difficult-to-treat pulmonary infections, particularly in individuals with cystic fibrosis (CF) and other underlying conditions. Its ability to form robust biofilms within the CF lung environment is a major factor contributing to its resistance to antibiotics and evasion of the host immune response, making conventional treatments largely ineffective. These biofilms, encased in an extracellular matrix, enhance drug tolerance and facilitate metabolic adaptations in hypoxic conditions, driving the bacteria into a persistent, non-replicative state that further exacerbates antimicrobial resistance. Treatment options remain limited, with multidrug regimens showing low success rates, highlighting the urgent need for more effective therapeutic strategies. Methods: In this study, we employed artificial sputum media to simulate the CF lung environment and conducted high-throughput screening of 24,000 compounds from diverse chemical libraries to identify inhibitors of MAB biofilm formation, using the Crystal Violet (CV) assay. Results: The screen established 17 hits with \u226530% biofilm inhibitory activity in mycobacteria. Six of these compounds inhibited MAB biofilm formation by over 60%, disrupted established biofilms by \u226540%, and significantly impaired bacterial viability within the biofilms, as confirmed by reduced CFU counts. In conformational assays, select compounds showed potent inhibitory activity in biofilms formed by clinical isolates of both MAB and Mycobacterium avium subsp. hominissuis (MAH). Key compounds, including ethacridine, phenothiazine, and fluorene derivatives, demonstrated potent activity against pre- and post-biofilm conditions, enhanced antibiotic efficacy, and reduced intracellular bacterial loads in macrophages. Conclusions: This study results underscore the potential of these compounds to target biofilm-associated resistance mechanisms, making them valuable candidates for use as adjuncts to existing therapies. These findings also emphasize the need for further investigations, including the initiation of a medicinal chemistry campaign to leverage structure\u2013activity relationship studies and optimize the biological activity of these underexplored class of compounds against nontuberculous mycobacterial (NTM) strains.<\/jats:p>","DOI":"10.3390\/ph18020225","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T04:00:28Z","timestamp":1738900828000},"page":"225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Discovery of Biofilm-Inhibiting Compounds to Enhance Antibiotic Effectiveness Against M. abscessus Infections"],"prefix":"10.3390","volume":"18","author":[{"given":"Elizaveta","family":"Dzalamidze","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mylene","family":"Gorzynski","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Vande Voorde","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dylan","family":"Nelson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1390-3121","authenticated-orcid":false,"given":"Lia","family":"Danelishvili","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA"},{"name":"Department of Microbiology, College of Science, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.3201\/2109.141634","article-title":"Mycobacterium abscessus Complex Infections in Humans","volume":"21","author":"Lee","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lopeman, R.C., Harrison, J., Desai, M., and Cox, J.A.G. (2019). Mycobacterium abscessus: Environmental Bacterium Turned Clinical Nightmare. Microorganisms, 7.","DOI":"10.20944\/preprints201901.0273.v1"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Honda, J.R., Virdi, R., and Chan, E.D. (2018). Global Environmental Nontuberculous Mycobacteria and Their Contemporaneous Man-Made and Natural Niches. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02029"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"00590-2020","DOI":"10.1183\/23120541.00590-2020","article-title":"Immune defects in patients with pulmonary Mycobacterium abscessus disease without cystic fibrosis","volume":"6","author":"Schuurbiers","year":"2020","journal-title":"ERJ Open Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1164\/rccm.200604-571ST","article-title":"An official ATS\/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases","volume":"175","author":"Griffith","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1093\/jac\/dkr578","article-title":"Mycobacterium abscessus: A new antibiotic nightmare","volume":"67","author":"Nessar","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"985","DOI":"10.2340\/00015555-2105","article-title":"Cutaneous infections caused by rapidly growing mycobacteria: Case reports and review of clinical and laboratory aspects","volume":"95","author":"Zhang","year":"2015","journal-title":"Acta Derm. Venereol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1055\/s-0033-1333567","article-title":"Update on the epidemiology of pulmonary nontuberculous mycobacterial infections","volume":"34","author":"Kendall","year":"2013","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ryan, K., and Byrd, T.F. (2018). Mycobacterium abscessus: Shapeshifter of the Mycobacterial World. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.02642"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/j.1600-0463.2006.apm_390.x","article-title":"Mycobacterium abscessus: An emerging rapid-growing potential pathogen","volume":"114","author":"Petrini","year":"2006","journal-title":"APMIS"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Keefe, B.F., and Bermudez, L.E. (2022). Environment in the lung of cystic fibrosis patients stimulates the expression of biofilm phenotype in Mycobacterium abscessus. J. Med. Microbiol., 71.","DOI":"10.1099\/jmm.0.001467"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1128\/AAC.00986-07","article-title":"Differential antibiotic susceptibility of Mycobacterium abscessus variants in biofilms and macrophages compared to that of planktonic bacteria","volume":"52","author":"Greendyke","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1183\/13993003.01102-2015","article-title":"Chronic pulmonary disease with Mycobacterium abscessus complex is a biofilm infection","volume":"46","author":"Qvist","year":"2015","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hunt-Serracin, A.C., Parks, B.J., Boll, J., and Boutte, C.C. (2019). Mycobacterium abscessus Cells Have Altered Antibiotic Tolerance and Surface Glycolipids in Artificial Cystic Fibrosis Sputum Medium. Antimicrob. Agents Chemother., 63.","DOI":"10.1128\/AAC.02488-18"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rojony, R., Danelishvili, L., Campeau, A., Wozniak, J.M., Gonzalez, D.J., and Bermudez, L.E. (2020). Exposure of Mycobacterium abscessus to Environmental Stress and Clinically Used Antibiotics Reveals Common Proteome Response among Pathogenic Mycobacteria. Microorganisms, 8.","DOI":"10.3390\/microorganisms8050698"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rojony, R., Martin, M., Campeau, A., Wozniak, J.M., Gonzalez, D.J., Jaiswal, P., Danelishvili, L., and Bermudez, L.E. (2019). Quantitative analysis of Mycobacterium avium subsp. hominissuis proteome in response to antibiotics and during exposure to different environmental conditions. Clin. Proteomics, 16.","DOI":"10.1186\/s12014-019-9260-2"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kurbatfinski, N., Hill, P.J., Tobin, N., Kramer, C.N., Wickham, J., Goodman, S.D., Hall-Stoodley, L., and Bakaletz, L.O. (2023). Disruption of nontuberculous mycobacteria biofilms induces a highly vulnerable to antibiotic killing phenotype. Biofilm, 6.","DOI":"10.1016\/j.bioflm.2023.100166"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105","DOI":"10.15698\/mic2019.02.667","article-title":"The extracellular matrix of mycobacterial biofilms: Could we shorten the treatment of mycobacterial infections?","volume":"6","author":"Chakraborty","year":"2019","journal-title":"Microb. Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1128\/IAI.00820-13","article-title":"Mycobacterium avium biofilm attenuates mononuclear phagocyte function by triggering hyperstimulation and apoptosis during early infection","volume":"82","author":"Rose","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1111\/j.1462-5822.2005.00667.x","article-title":"The ability to form biofilm influences Mycobacterium avium invasion and translocation of bronchial epithelial cells","volume":"8","author":"Yamazaki","year":"2006","journal-title":"Cell Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1128\/IAI.02699-14","article-title":"The environment of \u201cMycobacterium avium subsp. hominissuis\u201d microaggregates induces synthesis of small proteins associated with efficient infection of respiratory epithelial cells","volume":"83","author":"Babrak","year":"2015","journal-title":"Infect. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Uruen, C., Chopo-Escuin, G., Tommassen, J., Mainar-Jaime, R.C., and Arenas, J. (2020). Biofilms as Promoters of Bacterial Antibiotic Resistance and Tolerance. Antibiotics, 10.","DOI":"10.3390\/antibiotics10010003"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1128\/AAC.01509-15","article-title":"Biofilms of Pathogenic Nontuberculous Mycobacteria Targeted by New Therapeutic Approaches","volume":"60","author":"Aung","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1099\/mic.0.038794-0","article-title":"Quorum sensing in bacterial virulence","volume":"156","author":"Antunes","year":"2010","journal-title":"Microbiology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Boopathi, S., Ramasamy, S., Haridevamuthu, B., Murugan, R., Veerabadhran, M., Jia, A.Q., and Arockiaraj, J. (2022). Intercellular communication and social behaviors in mycobacteria. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.943278"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sharma, S., Mohler, J., Mahajan, S.D., Schwartz, S.A., Bruggemann, L., and Aalinkeel, R. (2023). Microbial Biofilm: A Review on Formation, Infection, Antibiotic Resistance, Control Measures, and Innovative Treatment. Microorganisms, 11.","DOI":"10.3390\/microorganisms11061614"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1080\/21505594.2017.1313372","article-title":"Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action","volume":"9","author":"Roy","year":"2018","journal-title":"Virulence"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hawas, S., Verderosa, A.D., and Totsika, M. (2022). Combination Therapies for Biofilm Inhibition and Eradication: A Comparative Review of Laboratory and Preclinical Studies. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.850030"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100133","DOI":"10.1016\/j.tcsw.2024.100133","article-title":"Combatting biofilm-mediated infections in clinical settings by targeting quorum sensing","volume":"12","author":"Mitra","year":"2024","journal-title":"Cell Surf."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1038\/s41467-020-14685-3","article-title":"Salmonella Typhimurium biofilm disruption by a human antibody that binds a pan-amyloid epitope on curli","volume":"11","author":"Tursi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/nchembio.242","article-title":"Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation","volume":"5","author":"Cegelski","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Silva, C., Rojony, R., Bermudez, L.E., and Danelishvili, L. (2020). Short-Chain Fatty Acids Promote Mycobacterium avium subsp. hominissuis Growth in Nutrient-Limited Environments and Influence Susceptibility to Antibiotics. Pathogens, 9.","DOI":"10.3390\/pathogens9090700"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Danelishvili, L., Shulzhenko, N., Chinison, J.J.J., Babrak, L., Hu, J., Morgun, A., Burrows, G., and Bermudez, L.E. (2017). Mycobacterium tuberculosis Proteome Response to Antituberculosis Compounds Reveals Metabolic \u201cEscape\u201d Pathways That Prolong Bacterial Survival. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.00430-17"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gupta, R., Netherton, M., Byrd, T.F., and Rohde, K.H. (2017). Reporter-Based Assays for High-Throughput Drug Screening against Mycobacterium abscessus. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.02204"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Richter, A., Strauch, A., Chao, J., Ko, M., and Av-Gay, Y. (2018). Screening of Preselected Libraries Targeting Mycobacterium abscessus for Drug Discovery. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.00828-18"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1164\/rccm.201508-1586IM","article-title":"Biofilm Formation by Mycobacterium abscessus in a Lung Cavity","volume":"193","author":"Fennelly","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e01212-19","DOI":"10.1128\/AAC.01212-19","article-title":"Biofilms of Mycobacterium abscessus Complex Can Be Sensitized to Antibiotics by Disaggregation and Oxygenation","volume":"64","author":"Kolpen","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"ofz221","DOI":"10.1093\/ofid\/ofz221","article-title":"Top Questions in the Diagnosis and Treatment of Pulmonary M. abscessus Disease","volume":"6","author":"Nathavitharana","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"511","DOI":"10.3201\/eid2203.150828","article-title":"Treatment of Mycobacterium abscessus Infection","volume":"22","author":"Novosad","year":"2016","journal-title":"Emerg. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1128\/AAC.01275-08","article-title":"A novel gene, erm(41), confers inducible macrolide resistance to clinical isolates of Mycobacterium abscessus but is absent from Mycobacterium chelonae","volume":"53","author":"Nash","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1093\/jac\/dku007","article-title":"Erm(41)-dependent inducible resistance to azithromycin and clarithromycin in clinical isolates of Mycobacterium abscessus","volume":"69","author":"Maurer","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jabri, T., Khan, N.A., Makhlouf, Z., Akbar, N., Gul, J., Shah, M.R., and Siddiqui, R. (2023). Antibacterial Properties of Ethacridine Lactate and Sulfmethoxazole Loaded Functionalized Graphene Oxide Nanocomposites. Antibiotics, 12.","DOI":"10.3390\/antibiotics12040755"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"25","DOI":"10.26502\/fjppr.049","article-title":"Anti-Mycobacterial and Synergistic Activity of Synthetic Acridine-9-Carboraldehyde and 9-Hydroxy-4-Methoxy Acridine Alkaloids against Clinical Isolates of Multidrug-Resistant Mycobacterium Tuberculosis","volume":"6","author":"Bunalema","year":"2022","journal-title":"J. Pharm. Pharmacol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Petrikaite, V., Tarasevicius, E., and Pavilonis, A. (2007). New ethacridine derivatives as the potential antifungal and antibacterial preparations. Medicina, 43.","DOI":"10.3390\/medicina43080084"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1111\/iwj.12057","article-title":"Efficacy of antiseptics containing povidone-iodine, octenidine dihydrochloride and ethacridine lactate against biofilm formed by Pseudomonas aeruginosa and Staphylococcus aureus measured with the novel biofilm-oriented antiseptics test","volume":"11","author":"Junka","year":"2014","journal-title":"Int. Wound J."},{"key":"ref_46","unstructured":"Garcia-Moreno, P.K. (2018). Mycobacterium tuberculosis inhibitors: Action and resistance. [Ph.D. Thesis, Florida International University]."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1128\/AAC.47.2.719-726.2003","article-title":"Phenothiazines and thioxanthenes inhibit multidrug efflux pump activity in Staphylococcus aureus","volume":"47","author":"Kaatz","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Vo, N., Sidner, B.S., Yu, Y., and Piepenbrink, K.H. (2023). Type IV Pilus-Mediated Inhibition of Acinetobacter baumannii Biofilm Formation by Phenothiazine Compounds. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.01023-23"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1742-7843.2005.pto960105.x","article-title":"In vitro activity of phenothiazine derivatives in Enterococcus faecalis and Enterococcus faecium","volume":"96","author":"Hendricks","year":"2005","journal-title":"Basic. Clin. Pharmacol. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Fiallos, N.M., Ribeiro Aguiar, A.L., da Silva, B.N., Pergentino, M.L.M., Rocha, M.F.G., Sidrim, J.J.C., Maia, D., and Cordeiro, R.A. (2022). The Potential of Phenothiazines against Endodontic Pathogens: A Focus on Enterococcus-Candida Dual-Species Biofilm. Antibiotics, 11.","DOI":"10.3390\/antibiotics11111562"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1093\/jac\/dks483","article-title":"Antitubercular pharmacodynamics of phenothiazines","volume":"68","author":"Warman","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41429-024-00731-5","article-title":"Miconazole and phenothiazine hinder the quorum sensing regulated virulence in Pseudomonas aeruginosa","volume":"77","author":"Gad","year":"2024","journal-title":"J. Antibiot."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1128\/AAC.01033-06","article-title":"Synergistic interaction between phenothiazines and antimicrobial agents against Burkholderia pseudomallei","volume":"51","author":"Chan","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1111\/jam.15109","article-title":"Antibacterial properties of phenothiazine derivatives against multidrug-resistant Acinetobacter baumannii strains","volume":"131","author":"Franco","year":"2021","journal-title":"J. Appl. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Vlad, I.M., Nuta, D.C., Ancuceanu, R.V., Caproiou, M.T., Dumitrascu, F., Marinas, I.C., Chifiriuc, M.C., Marutescu, L.G., Zarafu, I., and Papacocea, I.R. (2021). New O-Aryl-Carbamoyl-Oxymino-Fluorene Derivatives with MI-Crobicidal and Antibiofilm Activity Enhanced by Combination with Iron Oxide Nanoparticles. Molecules, 26.","DOI":"10.3390\/molecules26103002"},{"key":"ref_56","first-page":"745","article-title":"Synthesis of Novel Fluorene Bisamide Derivatives via Ugi Reaction and Evaluation their Biological Activity against Mycobacterium species","volume":"16","author":"Rezayan","year":"2017","journal-title":"Iran. J. Pharm. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e0047423","DOI":"10.1128\/aac.00474-23","article-title":"Discovery and characterization of antimycobacterial nitro-containing compounds with distinct mechanisms of action and in vivo efficacy","volume":"67","author":"Eke","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.ejmech.2015.06.035","article-title":"Design, synthesis and evaluation of new GEQ derivatives as inhibitors of InhA enzyme and Mycobacterium tuberculosis growth","volume":"101","author":"Chollet","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Ahmed, S., Manning, A., Flint, L., Awasthi, D., Ovechkina, Y., and Parish, T. (2021). Identification of Novel Chemical Scaffolds that Inhibit the Growth of Mycobacterium tuberculosis in Macrophages. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.790583"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"El-Gharably, A.A., Nassar, A.A., El-Ganzory, N.M., Saad-Allah, K.M., and El-Barbary, A.A. (2025). Sulfoxidation of pyrimidine thioate derivatives and study their biological activities. Sci. Rep., 15.","DOI":"10.1038\/s41598-024-83050-x"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1093\/nar\/26.8.1863","article-title":"Inhibition of DNA polymerase reactions by pyrimidine nucleotide analogues lacking the 2-keto group","volume":"26","author":"Guo","year":"1998","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Garg, S., Kumar, R., Kunimoto, D., and Rayat, G.R. (2022). Anti-Mycobacterial Activity of Flavonoid and Pyrimidine Compounds. Molecules, 27.","DOI":"10.3390\/molecules27196714"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.2174\/0929867311320100006","article-title":"Thymidylate kinase: An old topic brings new perspectives","volume":"20","author":"Cui","year":"2013","journal-title":"Curr. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5218","DOI":"10.2174\/0929867324666171009103327","article-title":"Benzothiazole-based Compounds in Antibacterial Drug Discovery","volume":"25","author":"Gjorgjieva","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s00044-023-03077-z","article-title":"Recent insights into antibacterial potential of benzothiazole derivatives","volume":"32","author":"Kashyap","year":"2023","journal-title":"Med. Chem. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"114333","DOI":"10.1016\/j.ejmech.2022.114333","article-title":"Novel benzothiazole\u2013urea hybrids: Design, synthesis and biological activity as potent anti-bacterial agents against MRSA","volume":"236","author":"Zha","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Carbone, A., Parrino, B., Cusimano, M.G., Spano, V., Montalbano, A., Barraja, P., Schillaci, D., Cirrincione, G., Diana, P., and Cascioferro, S. (2018). New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation. Mar. Drugs, 16.","DOI":"10.3390\/md16080274"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1093\/infdis\/165.1.75","article-title":"An animal model of Mycobacterium avium complex disseminated infection after colonization of the intestinal tract","volume":"165","author":"Bermudez","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8079","DOI":"10.1128\/JB.01138-07","article-title":"Nutritional cues control Pseudomonas aeruginosa multicellular behavior in cystic fibrosis sputum","volume":"189","author":"Palmer","year":"2007","journal-title":"J. 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