Click-based synthesis and antitubercular evaluation of dibenzofuran tethered thiazolyl-1,2,3-triazolyl acetamides.
A series of novel dibenzofuran tethered thiazolyl-1,2,3-triazolyl acetamides, designed by assembling antitubercular pharmacophoric fragments, dibenzofuran, 2-aminothiazole and substituted triazoles in one molecular architecture, were evaluated against Mycobacterium tuberculosis. The new analogues 6a-p accomplished in four step synthetic sequence utilizing click chemistry in the penultimate step, was fully characterized by their NMR and mass spectral data. Among the compounds 6a-p screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv, three compounds 6j (MIC: 1.56μg/mL); 6a and 6p (MIC: 3.13μg/mL) was found to be most active and exhibited lower cytotoxicity. Among these three, 6j could be a candidate to consider as a drug like hit analogue for further development.
Organic Chemistry Division-II (CPC Division), CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India.
Goverdhan
G
Surineni
Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, Telangana, India.
Perumal
P
Yogeeswari
Medicinal Chemistry and Antimycobacterial Research Laboratory, Pharmacy Group, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500078, Telangana, India.
Dharmarajan
D
Sriram
Organic Chemistry Division-II (CPC Division), CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, Telangana, India. Electronic address: kantevari@yahoo.com.
Srinivas
S
Kantevari
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D057930:Click Chemistry; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D000067996:RAW 264.7 Cells; D013329:Structure-Activity Relationship
D000081:Acetamides; D000995:Antitubercular Agents; D001572:Benzofurans; C023614:dibenzofuran
Antimycobacterial activity; Dibenzofuran; Thiazole; Triazole; Tuberculosis