Computational investigation of stigmasterol as a potential therapeutic agent for cervical cancer: insights from density functional theory (DFT) and molecular docking studies.

Abstract

Cervical cancer an appalling disease common amongst women worldwide, caused by human papillomavirus (HPV) with 80% increasing cases in developing countries, is reported to be persistent despite the various treatment measures. Hence, this research explores the properties of stigmasterol (SML), a biological active compound derived from Costus afer plant, as a drug agent for treatment of cervical cancer via density functional theory (DFT) studies and molecular docking investigation. Here, five key proteins were selected (for 4LEO, 7X8O, 5N2F, 4P7U and 2N5R) for in silico molecular docking study with SML. The DFT at ωB97XD/6-311++G (2d, 2p) level of theory was utilized and optimization of the compound was carried out in four different solvent phases, viz; acetone, ethanol, water, and gas to ascertain the level of reactivity and stability of the compound. The HOMO-LUMO energy gaps exhibited by acetone, ethanol, gas, and water were: 9.4128 eV, 9.4134 eV, 9.3140 eV, and 9.4164 eV, respectively. Interestingly, the resulting binding affinities for SML-protein interaction for 4LEO, 7X8O, 5N2F, 4P7U and 2N5R showed notable binding affinities of - 7.6 kcal/mol, - 5.2 kcal/mol, - 6.1 kcal/mol, - 5.2 kcal/mol and - 5.0 kcal/mol, respectively, as compared to the binding affinities (- 5.2 to - 7.6 kcal/mol) recorded for proteins-standard drugs interaction. The Non-covalent interactions (NCI) analysis showed predominately, van der Waals interactions in all the phases. This investigation suggest that SML can be used in the treatment and management of cervical cancer and requires further investigation.

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00361-1.