Selective synthesis of A-ring Е-arylidene derivatives from β-sitosterol and their activity

• Published in: Natural product research 2024-01, Vol.38 (1), p.52-59
• Main Authors: Petrova, A V, Khusnutdinova, E F, Lobov, A N, Zakirova, L M, Ha, N T T, Babkov, D A
• Format: Article
• Language: English
• Subjects: Acarbose; ADMET; alpha-Glucosidases - metabolism; arylidene; Cancer; Claisen-Schmidt reaction; Cytotoxicity; Diabetes mellitus; Glucosidase; Glycoside Hydrolase Inhibitors - chemistry; Hypoglycemic Agents - pharmacology; Magnetic resonance spectroscopy; Molecular Docking Simulation; Molecular Structure; Natural products; NMR spectroscopy; Steroids; Structure-Activity Relationship; α-Glucosidase; β-sitosterol
• ISSN: 1478-6419; 1478-6427
• DOI: 10.1080/14786419.2022.2103555

A series of 24-ethylcholest-4-ene-3,6-dione 2E-arylidene-derivatives has been synthesized by a Claisen-Schmidt reaction from a natural phytosterol β-sitosterol with yields of 80-85%. The structure of the obtained compounds was confirmed by NMR spectroscopy, including two-dimensional correlation experiments. The synthesized compounds were evaluated for their in vitro cytotoxicity and α-glucosidase inhibitory activity. It was established that compound 3 with pyridin-3-ylmethylene moiety exhibited a selective cytotoxic effect against the U251 cancer cell line with 99.31% inhibition of cancer cell growth. Compounds with pyridin-4-ylmethylene 4 and furan-2-ylmethylene-5 fragments were the most active inhibitors of α-glucosidase with IC 50 64.00 and 38.95 µM, being 3- and 5-times more active than acarbose. Binding mode to α-glucosidase and ADMET characteristics for the lead molecule 5 were proposed computationally. To sum up, an efficient approach to the derivatives with promising antidiabetic activity based on available natural product β-sitosterol is suggested.