Alkaloids Isolated from <i>Vepris glandulosa</i> with Antidiabetic Properties: An <i>In Vitro</i> and <i>In Silico</i> Analysis

Abstract

Diabetes is a major global health issue and as current treatments fail, the search for new antidiabetic drugs is crucial. This investigation, focusing on identifying potential antidiabetic compounds from the endangered plant species Vepris glandulosa, led to the isolation of two known alkaloids, choisyine acetate (1) and choisyine (2). The study established the in vitro inhibitory activities and in silico molecular interaction of the two alkaloids with α-amylase based on IC₅₀ values, Linewaever-Burk/Dixon plot kinetic analyses and Molecular docking, respectively. The α-amylase inhibition assay revealed noncompetitive inhibition for both compounds with IC₅₀ and Ki values of 4.74±0.17 and 4.75 mM for compound 1, and 11.29±0.44 and 12.37 mM for compound 2, respectively. In comparison, the standard drug acarbose displayed a competitive mode of inhibition, with IC₅₀ and Ki values of 11.99±0.02 and 12.68 mM, respectively. The binding affinities with α-amylase were -6.42 and -6.07 kcal/mol for compounds 1 and 2, respectively relative to acarbose -8.03 Kcal/mol. Moreover, these two compounds' predicted physicochemical and ADMET properties justified their potential as lead compounds for drug discovery. These compounds demonstrated remarkable inhibition potential comparable to the standard drug, highlighting their potential as viable alternatives in managing diabetes.