title: Rational design and synthesis of novel dibenzo[b,d]furan-1,2,3-triazole conjugates as potent inhibitors of Mycobacterium tuberculosis.
abstract: A series of novel dibenzo[b,d]furan-1,2,3-triazole conjugates, rationally designed by reorientation of dibenzo[b,d]furan pharmacophore and alkyl/aryl groups appended on 1,2,3-triazole core, were synthesized using click chemistry. The required key intermediate, 2-ethynyl dibenzo[b,d]furan 3 was prepared from dibenzofuran-2-carboxaldehyde using Corey-Fuchs reaction. Further reaction of 3 with various alkyl/aryl azides in the presence of copper catalyst produced 1,2,3-triazole conjugates in excellent yields. Evaluation of all the new compounds for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC27294), resulted 5a (MIC: 1.56 μg/mL), 5d (MIC: 0.78 μg/mL) and 5f (MIC: 0.78 μg/mL) as promising lead analogues. Among these three compounds, 1-(4-bromobenzyl)-4-(dibenzo[b,d]furan-2-yl)-1H-1,2,3-triazole (5f) emerged as the most promising antitubercular agent with lowest cytotoxicity (selectivity index: ≫25) against the HEK-293T cell line.
authors.affiliation: Organic Chemistry Division-II (CPC Division), CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Thirumal
authors.initials: T
authors.lastname: Yempala
authors.affiliation: Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India.
authors.forename: Jonnalagadda Padma
authors.initials: JP
authors.lastname: Sridevi
authors.affiliation: Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Organic Chemistry Division-II (CPC Division), CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India; Academy of Scientific and Innovative Research, CSIR- Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: kantevari@yahoo.com.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kantevari
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D057930:Click Chemistry; D057809:HEK293 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D001572:Benzofurans; D014230:Triazoles; C023614:dibenzofuran
keywords: Click chemistry; Corey–Fuchs reaction; Cytotoxicity; Dibenzofuran; Mycobacterium tuberculosis