Unveiling cervical cancer therapeutics from Abrus precatorius and Aphanamixis polystachya: Insights from molecular docking, dynamics simulation, MM/GBSA and DFT analyses

Abstract

Cervical cancer is the fourth most prevalent form of cancer affecting women, which poses a significant concern, especially in middle- and lower-income countries with an approximately 85 % fatality rate. As conventional drugs used to treat cervical cancer are expensive and expose severe side effects, there is a growing demand to search for novel medications. Therefore, in the current investigation employing bioinformatic approach, we explored bioactive phytoconstituents of two indigenous species of Bangladesh, namely Abrus precatorius L. and Aphanamixis polystachya (Wall.) R.N. Parker, for their anticancer efficacy targeting cervical cancer E6 oncoprotein. The study utilized molecular docking, ADMET assay, molecular dynamics simulation, MM/GBSA and DFT calculation that unveiled four lead compounds, such as Abruslactone A (-8.4 kcal/mol), Vitexin (-8.2 kcal/mol), 5-Betacholanic acid (-7.5 kcal/mol) and Pelargonidin 3-glucoside (-7.2 kcal/mol) from Abrus precatorius, and three lead compounds, namely Rohituka 5 (-7.5 kcal/mol), Polystachin (-7.5 kcal/mol) and Aphanamixinin (-7.3 kcal/mol) from Aphanamixis polystachya. All the lead candidates exhibited favorable pharmacokinetic, pharmacodynamic and toxicity properties. Molecular dynamics simulation revealed noteworthy structural stability and compactness of the lead candidates. MM/GBSA analysis unraveled Polystachin to have the highest free binding energy (-72.45 kcal/mol) and Abruslactone A having the lowest binding energy (-50.92 kcal/mol). DFT analysis revealed higher molecular reactivity of Aphanamixis polystachya phytocompounds than Abrus precatorius. Among the lead compounds, 5-Betacholanic acid showed the highest kinetic stability (ΔE = 7.217 eV), and Pelargonidin 3-glucoside demonstrated highest molecular reactivity (ΔE = 3.086 eV). The optimization of the lead compounds, assessment of safety profiles, and progression towards clinical trials could transform the current findings into promising drug candidates for cervical cancer. Finally, the results obtained from this study may lay the foundation for the development of novel anticancer therapeutics.