title: Development of antimycobacterial tetrahydrothieno[2,3-c]pyridine-3-carboxamides and hexahydrocycloocta[b]thiophene-3-carboxamides: Molecular modification from known antimycobacterial lead.
abstract: Twenty derivatives of 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxamide and ten of 2-substituted 4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide were synthesized by molecular modification of a known antimycobacterial molecule. Compounds were evaluated in vitro against Mycobacterium tuberculosis (MTB), and cytotoxicity against RAW 264.7 cell line. Among the compounds, 2-(4-phenoxybenzamido)-4,5,6,7,8,9-hexahydrocycloocta[b]thiophene-3-carboxamide (12f) was found to be the most active compound against MTB with MIC of 3.70 μM and was more potent than Ethambutol (MIC of 7.64 μM), Ciprofloxacin (MIC of 9.41 μM) and standard lead compound SID 92097880 (MIC of 9.15 μM). Compound 12f also showed MTB MIC of 1.23 μM in the presence of an efflux pump inhibitor verapamil, and showed no cytotoxicity at 50 μM.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, R.R. District, Hyderabad 500078, India.
authors.forename: Radhika
authors.initials: R
authors.lastname: Nallangi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, R.R. District, Hyderabad 500078, India.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Samala
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, R.R. District, Hyderabad 500078, India.
authors.forename: Jonnalagadda Padma
authors.initials: JP
authors.lastname: Sridevi
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, R.R. District, Hyderabad 500078, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Shameerpet, R.R. District, Hyderabad 500078, India. Electronic address: dsriram@hyderabad.bits-pilani.ac.in.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000995:Antitubercular Agents; D013876:Thiophenes
keywords: Cytotoxicity; Efflux pump; Hexahydrocycloocta[b]thiophene-3-carboxamides; Tetrahydrothieno[2,3-c]pyridine-3-carboxamides; Tuberculosis