Harnessing Nigeria's Biodiversity: A Computational Approach to Discovering Plant-Based Topoisomerase IIα Inhibitors

Abstract

This study uses a molecular docking approach to explore the potential of selected Nigerian anti-tumour plants as inhibitors of human topoisomerase IIα. Given the longstanding use of plant materials in traditional cancer treatments, this research leverages computational methods to elucidate the mechanisms of action of phytochemicals. Plant isolates were clustered with known topoisomerase IIα inhibitors to identify promising candidates. Molecular docking simulations were performed using an enzyme complexed with DNA, revealing binding affinities of various compounds. The results indicated that most compounds with high similarity to known inhibitors originated from Olea europea and Cadaba farinosa. Notably, cadabacine diacetate exhibited the lowest binding energy, while 3(4-formylphenoxy)-4 methoxybenzaldehyde presented the highest. Compounds such as Apigenin-7-O-glucoside and suspensaside demonstrated higher affinity for topoisomerase IIα compared to etoposide, suggesting their potential as effective inhibitors. Additionally, rutin also showed significant affinity, while secologanoside presented the highest binding energy with topoisomerase IIb. The findings highlight the efficacy of molecular docking in identifying potential anti-cancer agents derived from indigenous plants. However, further studies on the structure-activity relationships (SAR) of these compounds are essential to ascertain their therapeutic potential. This research underscores the importance of combining traditional knowledge with modern computational techniques in the pursuit of novel cancer therapies.