Design, synthesis, characterization, and anti-tubercular activity of novel ethyl-3-benzoyl-6, 8-difluoroindolizine-1-carboxylate analogues: Molecular target identification and molecular docking studies

Hu, 2017, Prevalence and molecular characterization of second-line drugs resistance among multidrug-resistant Mycobacterium tuberculosis isolates in southwest of China, Biomed. Res. Int., 10.1155/2017/4563826 Ravimohan, 2018, Tuberculosis and lung damage: from epidemiology to pathophysiology, Eur. Respir. Rev., 27, 10.1183/16000617.0077-2017 Global Tuberculosis report WHO 2020, (2020). 2022 Dheda, 2010, Early treatment outcomes and HIV status of patients with extensively drug-resistant tuberculosis in South Africa: a retrospective cohort study, Lancet, 375, 1798, 10.1016/S0140-6736(10)60492-8 Hameed, 2018, Molecular targets related drug resistance mechanisms in MDR-, XDR-, and TDR-Mycobacterium tuberculosis strains, Front. Cell. Infect. Microbiol., 8, 114, 10.3389/fcimb.2018.00114 Wang, 2021, Efficacy of bedaquiline in the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis, BMC Infect. Dis., 21, 970, 10.1186/s12879-021-06666-8 van Heeswijk, 2014, Bedaquiline: a review of human pharmacokinetics and drug-drug interactions, J. Antimicrob. Chemother., 69, 2310, 10.1093/jac/dku171 Nguyen, 2018, Bedaquiline resistance: its emergence, mechanism, and prevention, Clin. Infect. Dis., 66, 1625, 10.1093/cid/cix992 Fujiwara, 2018, Mechanisms of resistance to delamanid, a drug for Mycobacterium tuberculosis, Tuberculosis (Edinb), 108, 186, 10.1016/j.tube.2017.12.006 Keam, 2019, Pretomanid: first approval, Drugs, 79, 1797, 10.1007/s40265-019-01207-9 Tetali, 2020, Current advances in the clinical development of anti-tubercular agents, Tuberculosis (Edinb), 125, 10.1016/j.tube.2020.101989 Yee, 2003, Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis, Am. J. Respir. Crit. Care Med., 167, 1472, 10.1164/rccm.200206-626OC Gruber, 2020, Introduction: Novel insights into TB research and drug discovery, Prog. Biophys. Mol. Biol., 152, 2, 10.1016/j.pbiomolbio.2020.02.003 Shirude, 2013, Azaindoles: noncovalent DprE1 inhibitors from scaffold morphing efforts, kill Mycobacterium tuberculosis and are efficacious in vivo, J. Med. Chem., 56, 9701, 10.1021/jm401382v Katherine A Sacksteder, 2013, Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action, Future Microbiol., 07, 823, 10.2217/fmb.12.56 Stelitano, 2020, Multitargeting compounds: a promising strategy to overcome multi-drug resistant tuberculosis, Molecules, 25, 10.3390/molecules25051239 Hosseini, 2018, Polypharmacy among the Elderly, J. Midlife Health, 9, 97 Li, 2014, Novel insights into the mechanism of inhibition of MmpL3, a target of multiple pharmacophores in Mycobacterium tuberculosis, Antimicrob. Agents Chemother., 58, 6413, 10.1128/AAC.03229-14 Ganihigama, 2015, Antimycobacterial activity of natural products and synthetic agents: pyrrolodiquinolines and vermelhotin as anti-tubercular leads against clinical multidrug resistant isolates of Mycobacterium tuberculosis, Eur. J. Med. Chem., 89, 1, 10.1016/j.ejmech.2014.10.026 Khedr, 2018, Molecular modeling studies and anti-TB activity of trisubstituted indolizine analogues; molecular docking and dynamic inputs, J. Biomol. Struct. Dyn., 36, 2163, 10.1080/07391102.2017.1345325 Venugopala, 2019, Computational, crystallographic studies, cytotoxicity and anti-tubercular activity of substituted 7-methoxy-indolizine analogues, PLoS One, 14, 10.1371/journal.pone.0217270 Venugopala, 2019, Anti-tubercular activity of substituted 7-methyl and 7-formylindolizines and in silico study for prospective molecular target identification, Antibiotics (Basel), 8 Weide, 2006, 3-substituted indolizine-1-carbonitrile derivatives as phosphatase inhibitors, Bioorg. Med. Chem. Lett., 16, 59, 10.1016/j.bmcl.2005.09.051 Olaru, 2017, Mangalagiu, II, antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII(8–12), J. Enzyme Inhib. Med. Chem., 32, 1291, 10.1080/14756366.2017.1375483 Gundersen, 2007, Synthesis of indolizine derivatives with selective antibacterial activity against Mycobacterium tuberculosis, Eur. J. Pharm. Sci., 30, 26, 10.1016/j.ejps.2006.09.006 Sandeep, 2013, Efficient synthesis of indolizines and new imidazo[1,2-a]pyridines via the expected cyclization of aromatic cycloimmonium ylides with electron deficient alkynes and ethyl cyanoformate, Tetrahedron. Lett., 54, 6411, 10.1016/j.tetlet.2013.09.033 Venugopala, 2018, Efficient synthesis and characterization of novel substituted 3-benzoylindolizine analogues via the cyclization of aromatic cycloimmoniumylides with electrondeficient alkenes, Curr. Org. Synth., 15, 388, 10.2174/1570179414666171024155051 Sandeep, 2014, Synthesis of Substituted 5-acetyl-3-benzoylindolizine-1-carboxylate from substituted 2-acetyl pyridinium bromides, Heterocycl. Lett., 04, 371 Venugopala, 2019, Novel series of methyl 3-(substituted benzoyl)-7-substituted-2-phenylindolizine-1-carboxylates as promising anti-inflammatory agents: molecular modeling studies, Biomolecules, 9, 10.3390/biom9110661 Sandeep, 2016, Synthesis and characterization of ethyl 7-acetyl-2-substituted 3-(substituted benzoyl)indolizine-1-carboxylates for in vitro anticancer activity, Asian J. Chem., 28, 1043, 10.14233/ajchem.2016.19582 Chandrashekharappa, 2018, Efficient synthesis and characterization of novel indolizines: exploration of in vitro COX-2 inhibitory activity and molecular modelling studies, N. J. Chem., 42, 4893, 10.1039/C7NJ05010K Sandeep, 2017, Design and synthesis of novel indolizine analogues as COX-2 inhibitors: computational perspective and in vitro screening, Indian J. Pharm. Educ. Res., 51, 452, 10.5530/ijper.51.3.73 Venugopala, 2021, Crystallography, molecular modeling, and COX-2 inhibition studies on indolizine derivatives, Molecules, 26, 10.3390/molecules26123550 Sandeep, 2013, Synthesis of isomeric subtituted 6-acetyl-3-benzoylindolizine-1-carboxylate and 8-acetyl-3-benzoylindolizine-1-carboxylate from subtituteded 3-acetyl pyridinium bromides and their antimicrobial activity, J. Appl. Chem., 2, 1049 Chandrashekharappa, 2019, Qualitative anti-tubercular activity of synthetic ethyl 7-acetyl2-substituted-3-(4-substituted benzoyl) indolizine-1-carboxylate analogues, J. Appl. Pharm. Sci., 9, 124, 10.7324/JAPS.2019.90217 Venugopala, 2021, Anti-tubercular activity and molecular docking studies of indolizine derivatives targeting mycobacterial InhA enzyme, J. Enzyme Inhib. Med. Chem., 36, 1472, 10.1080/14756366.2021.1919889 Chandrashekharappa, 2018, One-pot microwave assisted synthesis and structural elucidation of novel ethyl 3-substituted-7-methylindolizine-1-carboxylates with larvicidal activity against Anopheles arabiensis, J. Mol. Struct., 1156, 377, 10.1016/j.molstruc.2017.11.131 Sandeep, 2016, Greener synthesis of indolizine analogues using water as a base and solvent: study for larvicidal activity against Anopheles arabiensis, Chem. Biol. Drug Des., 88, 899, 10.1111/cbdd.12823 Alwassil, 2019, Design, synthesis, and structural elucidation of novel NmeNANAS inhibitors for the treatment of meningococcal infection, PLoS One, 14, 10.1371/journal.pone.0223413 Dawood, 2020, Inhibitory activities of indolizine derivatives: a patent review, Expert Opin. Ther. Pat., 30, 695, 10.1080/13543776.2020.1798402 Singh, 2011, Recent progress in synthesis and bioactivity studies of indolizines, Eur. J. Med. Chem., 46, 5237, 10.1016/j.ejmech.2011.08.042 C, 2017, Review on chemistry of natural and synthetic indolizines withtheir chemical and pharmacological properties, J. Basic Clin. Pharm., 8, 49 Venugopala, 2020, Cytotoxicity and antimycobacterial properties of pyrrolo[1,2-a]quinoline derivatives: molecular target identification and molecular docking studies, Antibiotics (Basel), 9 Venugopala, 2020, In silico design and synthesis of tetrahydropyrimidinones and tetrahydropyrimidinethiones as potential thymidylate kinase inhibitors exerting anti-TB activity against Mycobacterium tuberculosis, Drug Des. Dev. Ther., 14, 1027, 10.2147/DDDT.S228381 Venugopala, 2019, Benzothiazole analogs as potential anti-TB agents: computational input and molecular dynamics, J. Biomol. Struct. Dyn., 37, 1830, 10.1080/07391102.2018.1470035 Venugopala, 2019, Anti-tubercular potency and computationallyassessed drug-likeness and toxicology of diversely substituted indolizines, Indian J. Pharm. Educ. Res., 53, 545, 10.5530/ijper.53.3.87 Danac, 2014, Antimycobacterial activity of nitrogen heterocycles derivatives: bipyridine derivatives. Part III, Eur. J. Med. Chem., 74, 664, 10.1016/j.ejmech.2013.09.061 Danac, 2015, Mangalagiu, II, new indolizines with phenanthroline skeleton: synthesis, structure, antimycobacterial and anticancer evaluation, Bioorg. Med. Chem., 23, 2318, 10.1016/j.bmc.2015.03.077 Hazra, 2011, Amberlite-IRA-402 (OH) ion exchange resin mediated synthesis of indolizines, pyrrolo [1,2-a] quinolines and isoquinolines: antibacterial and antifungal evaluation of the products, Eur. J. Med. Chem., 46, 2132, 10.1016/j.ejmech.2011.02.066 Saqib Kidwai, 2017, Dual mechanism of action of 5-nitro-1,10-phenanthroline against Mycobacterium tuberculosis, Antimicrob. Agents Chemother., 61, e00969