Solacanin C, a new pregnane steroid from Solanum torvum fruits: structural elucidation, potent α-glucosidase inhibition, and in silico ADMET profiling

Abstract

Fractionation of the ethyl acetate extract of unripe Solanum torvum Swartz fruits led to the isolation of a new pregnane-type steroid, solacanin C (1), together with six known steroidal compounds. Their chemical structures were elucidated using comprehensive spectroscopic analyses, including 1D- and 2D-NMR, FTIR, HRESIMS, and ECD calculations to determine absolute configurations. In vitro anti-α-glucosidase evaluation indicated that compounds 1–4 and 6 exhibited potent inhibitory activity (IC50; 2.0–12.8 µM), with debenzoylcarpesterol (6) being the most active. Molecular docking simulations with yeast α-glucosidase MAL12 confirmed that these isolated steroids occupy the hydrophobic catalytic cleft, forming key hydrogen bonds with residues Arg312, Arg439, and Asp349. Structure–activity relationship analysis indicated that a free 3β-hydroxyl group and moderate glycosylation enhance potency, while bulky acyl groups or long oligosaccharide chains reduce activity due to steric hindrance. In silico ADMET profiling further highlighted the therapeutic potential of the isolated leads. The new steroid solacanin C (1) demonstrated the most balanced medicinal chemistry profile with high drug-likeness (QED) and full compliance with Lipinski's rules, while 6 exhibited superior oral bioavailability F50% and high Caco-2 permeability. Both compounds showed low predicted toxicity, suggesting that the compact pregnane scaffold of 1 and the optimized cholestane framework of 6 provide robust foundations for the development of natural α-glucosidase inhibitors in type 2 diabetes management.