Exploring Anti-diabetic Activity of <i>Xylopia aethiopica</i> Compounds as Potential Inhibitors of α-Amylase and α-Glucosidase: Experimental and Computational Approach

Background Diabetes mellitus is marked with hyperglycemia due to insulin impairment and could be managed with α-glucosidase inhibitors, known to have side effects. Therefore, this study profiled the in vitro anti-diabetic activity of Xylopia aethiopica seeds, isolated and characterized its compounds, and in silico profiled these ligands against α-amylase and α-glucosidase to ascertain their benefit-to-risk ratio. Methods The extraction, isolation, characterization, evaluation of anti-diabetic activity, investigation of the extract's anti-proliferative activity against the breast cancer cell line (MCF7), retrieval of α-amylase and α-glucosidase, ADMET, and docking studies were done according to standard protocols; eluents were isolated and characterized using thin layer and column chromatography, and GC-MS; pharmacokinetic properties were evaluated with the help of PKCSM and ADMET Lab 2 tools; docking analysis was performed using PyRx; Biovia Discovery Studio for 2D visualization; and PyMol software for 3D visualization of the ligand-protein interactions. Results After 72 h, the extract's cytotoxic value against the MCF-7 cell line was 57.03 μg/mL. Additionally, the extract (0.15) and (1.13) had the best inhibitory activity (IC 50 ) (µg/ml) of α-amylase and α-glucosidase in a dose-dependent manner when compared favorably with acarbose (0.12) and (1.09), respectively. The chromatographic analyses yielded bulked fractions (A-D); fraction C (2135 mg) was further semi-purified to sub-fractions C2 (AS3) (17 mg), C4 (AS8) (21 mg), and C7 (AS11) (26 mg), and yielded xanthumin, metolachlor, Z-10-tetradecen-1-ol acetate, 13-docosenoic acid methyl ester, and alpha-bisabolol with reported anti-diabetic activities after GC-MS analysis. Docking with 7K9N and 3BC9 revealed the binding affinities (kcal/mol) of 1-Chlorotetradecane (−5.8) as well as 1-Chlorotetradecane (−5.2); 1-(4-Bromobutyl)-2-piperidinone (5.0); and 11,12-Dibromo-tetradecan-1-ol acetate (5.0) as the best when compared with metformin (−4.4, −3.7), respectively. All the compounds obeyed Lipinski's criteria, showed inactivity to hepatotoxicity, carcinogenicity, and immunotoxicity, and were non-inhibitors of mono-oxygenases. Conclusion These ligands’ better antineoplastic potency, pharmacokinetic, binding affinities, physicochemical, and drug-like properties as compared to metformin and acarbose drugs imply they could control hyperglycemia with a higher benefit-to-risk ratio; hence, their potential as lead compounds for the production of anti-diabetic drugs.