Cytotoxic, Apoptotic, and Molecular Docking Analysis of Bioactive Compounds from Plectronia Parviflora for Anticancer Potential

Abstract

Cervical cancer remains a leading cause of cancer-related mortality among women globally, necessitating the exploration of novel therapeutics with improved efficacy and safety. The present study investigates the anticancer potential of bioactive phytoconstituents isolated from Plectronia Parviflora, namely kaempferol 3-O-β-D-glucopyranoside and (25S)-5β-spirostan-3β-yl β-D-glucoside. Using chromatographic (HPTLC) and spectroscopic (¹H and ¹³C NMR) techniques, these compounds were isolated and structurally characterized from hydroalcoholic leaf extracts. In vitro cytotoxicity on HeLa cervical cancer cell lines was evaluated using MTT assays, revealing significant dose-dependent inhibition of cell viability. Flow cytometry analysis confirmed enhanced early and late apoptotic cell populations upon treatment.

In silico investigations were conducted to explore molecular interactions with tubulin (PDB ID: 4O2B), employing molecular docking, molecular dynamics simulations, and MM-PBSA binding free energy calculations. Both compounds showed strong tubulin binding affinities, with kaempferol 3-O-β-D-glucopyranoside exhibiting the highest stability. ADMET modelling further supported their drug-likeness, particularly for (25S)-5β-spirostan-3β-yl β-D-glucoside, which demonstrated favorable gastrointestinal absorption and blood-brain barrier permeability.

Network pharmacology revealed key target proteins such as TUBA1A and EGFR, central to cervical cancer pathways. The findings suggest that the tested compounds exert their anticancer effects by modulating microtubule dynamics and inducing apoptosis, positioning them as promising leads for further drug development.

This study underscores the therapeutic potential of Plectronia Parviflora phytochemicals in developing targeted, low-toxicity treatments for cervical cancer.