Potential protein antiglycation, antiproliferation, and in silico study on the antidiabetic enzymes of bioactive metabolites from Adonis microcarpa DC and their ADMET properties

Abstract

Adonis microcarpa DC has not been comprehensively studied for its phytochemical and biological properties. The phytochemical investigation of the above-ground parts led to the isolation of adonitol (1), lup-20(29)-en-3β-ol (2), 3β-3-hydroxyolean-12-en-28-oate (3), strophanthidin-3-O-β-D-glucopyranosyl-(1→4)-β-D-digitoxoside (4), strophanthidin-3-O-β-glucopyranosyl-(1→4)-β-boiviopyranoside (5) and gluco-(1→6)-strophanthidin-3-O-β-glucopyranosyl-(1→4)-β-boiviopyranoside (6). Their structures were assigned based on extensive 1D- and 2D-nuclear magnetic resonance spectral analyses. All the compounds are isolated for the first time from this species. Compounds 2 and 3 revealed high potency as antiglycated agents. The docking study introduced α-amylase as a preferable candidate for inhibition compared to α-glucosidase, with a slight superiority of 3. Aldose reductase was inhibited by 2 in a noncompetitive manner, while 3 probably was inactive toward it. Molecular docking suggested the activity of 2 and 3 as the possible inhibitors of α-glucosidase and α-amylase, while aldose reductase is an additional target of 2 by an allosteric effect. In silico physicochemical properties, such as absorption, distribution, metabolism, excretion, and toxicity parameters, of compounds were also predicted. Compounds 1, 2, and 3 were favorable in an acceptable prediction. The antiproliferative potentials on six human cancer cell lines in addition to a normal human lung fibroblast (WI-38) were carried out. Cell viability was evaluated and both triterpenoids have not exerted any cytotoxicity on the tested normal cell line. Interestingly, compound 3 rather than 2 introduced a considerable antiproliferative effect against the tested colon cancer cell lines.