Synthesis and biological evaluation of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thioglycosides

• Published in: Bioorganic & medicinal chemistry letters 2017-08, Vol.27 (15), p.3370-3373
• Main Authors: Vudhgiri, Srikanth, Koude, Dhevendar, Veeragoni, Dileep Kumar, Misra, Sunil, Prasad, R.B.N., Jala, Ram Chandra Reddy
• Format: Article
• Language: English
• Subjects: 1, 3, 4-Thiadiazole; Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antimicrobial; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Proliferation - drug effects; CHO Cells; Cricetulus; Cytotoxicity; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Fatty acids; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Microbial Sensitivity Tests; Molecular Structure; Structure-Activity Relationship; Thioglycoside; Thioglycosides - chemical synthesis; Thioglycosides - chemistry; Thioglycosides - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.06.004

[Display omitted] In the present study, the synthesis of 1, 3, 4-thiadiazole-based thioglycosides were accomplished in good yields with employing a convergent synthetic route. The starting material 5-amino-1, 3, 4-thiadiazole-2-thiol and followed by a series of 5-fatty-acylamido-1, 3, 4-thiadiazole-2-thiols (4a–4j) were synthesized with different fatty acid chlorides. The glycosylation of compounds 4a–4j were achieved with trichloroacetimidate methodology. Antimicrobial and cytotoxicity activities of title compounds were evaluated. Among the entire compounds lauric acid and myristic acid derivatives showed good and moderate antimicrobial activity. In case of cytotoxicity results of compounds 8a–8j and 9a–9j, the acetate protected short chain (C6:0, C8:0, C10:0) compounds and the free hydroxyl long chain saturated (C16:0, C18:0) and unsaturated (C18:1, C22:1) compounds exhibited good activity against different cancer cell lines. Further, the free hydroxyl compounds 9a, 9c–9j did not show any toxicity towards normal CHO-K1 cell line whereas acylated compounds 8a–8j exhibited toxicity.