title: Design, synthesis, and structure-activity correlations of novel dibenzo[b,d]furan, dibenzo[b,d]thiophene, and N-methylcarbazole clubbed 1,2,3-triazoles as potent inhibitors of Mycobacterium tuberculosis.
abstract: A molecular hybridization approach is an emerging structural modification tool to design new molecules with improved pharmacophoric properties. In this study, 1,2,3-triazole-based Mycobacterium tuberculosis inhibitors and synthetic and natural product-based tricyclic (carbazole, dibenzo[b,d]furan, and dibenzo[b,d]thiophene) antimycobacterial agents were integrated in one molecular platform to prepare various novel clubbed 1,2,3-triazole hybrids using click chemistry. Structure-activity correlations and in vitro activity against M. tuberculosis strain H37Rv of new analogues revealed the order: dibenzo[b,d]thiophene > dibenzo[b,d]furan > 9-methyl-9H-carbazole series. Two of the most potent M. tuberculosis inhibitors 13h and 13q with MIC = 0.78 μg/mL (∼1.9 μM) displayed a low cytotoxicity and high selectivity index (50-255) against four different human cancer cell lines. These results together provided the potential importance of molecular hybridization and the development of triazole clubbed dibenzo[b,d]thiophene-based lead candidates to treat mycobacterial infections.
authors.affiliation: Organic Chemistry (CPC) Division-II, Indian Institute of Chemical Technology, Hyderabad-500607, India.
authors.forename: Santhosh Reddy
authors.initials: SR
authors.lastname: Patpi
authors.forename: Lokesh
authors.initials: L
authors.lastname: Pulipati
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.forename: Nishant
authors.initials: N
authors.lastname: Jain
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Sridhar
authors.forename: Ramalinga
authors.initials: R
authors.lastname: Murthy
authors.forename: T
authors.initials: T
authors.lastname: Anjana Devi
authors.forename: Shasi Vardhan
authors.initials: SV
authors.lastname: Kalivendi
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kantevari
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis*; D045744:Cell Line, Tumor; D057930:Click Chemistry; D054697:Cytostatic Agents / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013876:Thiophenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D001572:Benzofurans; D002227:Carbazoles; D054697:Cytostatic Agents; D013876:Thiophenes; D014230:Triazoles; C023614:dibenzofuran; C016366:dibenzothiophene