Click-based synthesis and antitubercular evaluation of dibenzofuran tethered thiazolyl-1,2,3-triazolyl acetamides

• Published in: Bioorganic & medicinal chemistry letters Vol. 26; no. 15; pp. 3684 - 3689
• Main Authors: Surineni, Goverdhan, Yogeeswari, Perumal, Sriram, Dharmarajan, Kantevari, Srinivas
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.08.2016; Elsevier
• Subjects: Acetamides - chemical synthesis; Acetamides - chemistry; Acetamides - pharmacology; Animals; Antimycobacterial activity; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - pharmacology; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Click Chemistry; Dibenzofuran; Dose-Response Relationship, Drug; Life Sciences & Biomedicine; Mice; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Pharmacology & Pharmacy; Physical Sciences; RAW 264.7 Cells; Science & Technology; Structure-Activity Relationship; Thiazole; Triazole; Tuberculosis; Triazole; Tuberculosis; Thiazole; Antimycobacterial activity; Dibenzofuran; MYCOBACTERIUM-TUBERCULOSIS; TYROSINE-PHOSPHATASE B; ACID; PERSPECTIVE; DRUG DISCOVERY; TOXICITY; POTENT INHIBITORS; DERIVATIVES; RATIONAL DESIGN
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.05.085

[Display omitted] 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.