α-Glucosidase inhibitory activities of flavonoid derivatives isolated from Bouea macrophylla: in vitro and in silico studies

Abstract

In continuation of our search for bioactive compounds from the Bouea macrophylla (B. macrophylla) plant, we describe herein eight flavonoid-type compounds including mearsetin (1), mearnsitrin (2), kampferol (3), afzelin (4), quercetin (5), quercitrin (6), myricitin (7), and naringenin (8) with the aim of investigating their antidiabetic properties. Compounds 3 and 5 were selected for aromatic bromination to provide two new products 3a and 5a, respectively. All compounds showed promising α-glucosidase inhibition, with IC₅₀ values ranging from 9.2 to 266 μM apart from compound (2). Remarkably, compound 5a, 8-bromoquercetin, showed the highest inhibition activity, and it was thirty-seven times better than the standard drug acarbose. Pose 261/compound 5a interacted well with enzyme 3TOP in silico docking, and the complex of pose 261 and target enzyme proved its stability in MD. Compound 5a, pose 261 was predicted to be safe and seemed to have good absorption, distribution, metabolism, and excretion properties as assessed via the ADMET model in silico. Our findings revealed the α-glucosidase inhibitory potential of the flavonoids isolated from the leaves of B. macrophylla with a predictive pharmacokinetics profile, which may be helpful in their development as potential drugs.