title: Thiazole-aminopiperidine hybrid analogues: design and synthesis of novel Mycobacterium tuberculosis GyrB inhibitors.
abstract: A series of ethyl-4-(4-((substituted benzyl)amino)piperidin-1-yl)-2-(phenyl/pyridyl)thiazole-5-carboxylates was designed by molecular hybridization and synthesized from aryl thioamides in five steps. The compounds were evaluated for their in vitro Mycobacterium smegmatis (MS) GyrB ATPase assay, Mycobacterium tuberculosis (MTB) DNA gyrase super coiling assay, antituberculosis activity and cytotoxicity. Among the twenty four compounds studied, ethyl-4-(4-((4-fluorobenzyl)amino)piperidin-1-yl)-2-phenylthiazole-5-carboxylate (14) was found to be the promising compound which showed activity against all test with MS GyrB IC50 of 24.0 ± 2.1 μM, 79% inhibition of MTB DNA gyrase at 50 μM, MTB MIC of 28.44 μM, and not cytotoxic at 50 μM.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, R.R. District, Hyderabad 500078, Andhra Pradesh, India.
authors.forename: Variam Ullas
authors.initials: VU
authors.lastname: Jeankumar
authors.forename: Janupally
authors.initials: J
authors.lastname: Renuka
authors.forename: Peddi
authors.initials: P
authors.lastname: Santosh
authors.forename: Vijay
authors.initials: V
authors.lastname: Soni
authors.forename: Jonnalagadda Padma
authors.initials: JP
authors.lastname: Sridevi
authors.forename: Priyanka
authors.initials: P
authors.lastname: Suryadevara
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D027081:DNA Gyrase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D010880:Piperidines; D013844:Thiazoles; D059005:Topoisomerase II Inhibitors; D027081:DNA Gyrase
keywords: Amino piperidine; DNA gyrase; GyrB subunit; Thiazole; Tuberculosis