Synthesis of New Valinol‐Derived Sultam Triazoles as α‐Glucosidase Inhibitors

• Published in: ChemistrySelect (Weinheim) 2021-10, Vol.6 (37), p.9780-9786
• Main Authors: Jaffery, Syeda Mehak Fatima, Khan, Maria Aqeel, Ullah, Saeed, Atia‐tul‐Wahab, Choudhary, Muhammad Iqbal, Basha, Fatima Zehra
• Format: Article
• Language: English
• Subjects: Click chemistry; Diabetes; Heterocycles; Sultam triazoles; α-Glucosidase inhibitors
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202102119

α‐Glucosidase inhibition is one of the key targets for controlling diabetes. In consideration of that, new L‐valinol derived fluorinated sultam triazoles were synthesized as α‐glucosidase inhibitors, and their activities were further compared with the precursor molecules (sulfonamides, sultams, and N‐propargyl sultams). Primarily, all the synthesized sultam triazoles and precursor compounds (sulfonamides, sultams, and N‐propargyl sultams) were evaluated for different biological activities, including cytotoxicity, anti‐inflammatory, and α‐glucosidase inhibitory activities. Results revealed that only sultam triazoles exhibited inhibition against α‐glucosidase enzyme (IC50 values: 173 to 194 μM) using acarbose (IC50: 875.85 ± 2.03 μM) as the standard drug. These sultam triazoles were prepared after few steps, starting from enantiopure L‐valinol, which differ electronically (due to the position of fluorine atom and different positions on aromatic ring). Structures of all the compounds were evaluated using different spectroscopic techniques. Kinetics of active compounds were also investigated to find their mode of inhibition. A small library of sultam triazoles was prepared, and was evaluated for in vitro α‐glucosidase inhibitory activity. Synthesized compounds were compared with their precursor molecules for the activity and results showed that only triazole compounds were found to inhibit α‐glucosidase enzyme.