Computational Evaluation of Indole Alkaloids from Rauwolfia vomitoria as Potential Anticancer Agents: Molecular Docking and ADME Profiling
Nzube F. Ekpunobi *
Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria.
Sandra C. Okoye
Department of Biological Sciences, College of Liberal Arts and Sciences, Eastern Illinois University, Charleston, USA.
Eddison I. Oghonyon
Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, David Umahi Federal University of Health Sciences, Uburu, Ebonyi State, Nigeria.
Chidimma R. Chukwunwejim
Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Awka, Nigeria.
Merylann A. Ochieng
Department of Biological Sciences, College of Liberal Arts and Sciences, Eastern Illinois University, Charleston, USA.
Oluwatosin T. Idowu
Department of Medical Laboratory Sciences, College of Medicine, University of Lagos, Lagos, Nigeria.
Sabbath Usen-Obong
Department of Health Economics, Management and Policy, Global Health and Infectious Disease Control Institute (GHIDI), Nasarawa State University, Keffi, Nigeria.
Matthew O. Olushola
Department of Microbiology, Faculty of science, Olabisi Onabanjo University, Ogun State, Nigeria.
Agu, K.C
Department of Applied Microbiology and Brewing, Faculty of Biosciences, Nnamdi Azikiwe University, Awka, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Background: Cancer continues to pose a major global health challenge, particularly in low- and middle-income countries, where treatment costs and accessibility remain limiting. Natural products such as Rauwolfia vomitoria have shown significant promise as alternative sources of bioactive anticancer compounds. This study evaluated the anticancer potential of two key indole alkaloids—Ajmalicine and Alstonine—through molecular docking and in silico pharmacokinetic and toxicity profiling.
Methods: A computational approach was employed using Schrödinger Maestro Suite (2023-3) for docking simulations, SwissADME for ADMET analysis, and ProTox-III for toxicity prediction. Six cancer-associated targets—BCL-2, PI3K, EGFR, STAT3, HDAC, and NF-κB—were selected to compare binding affinities and drug-likeness properties of the alkaloids against known inhibitors.
Results: Both compounds exhibited favorable pharmacokinetic profiles with high gastrointestinal absorption and good drug-likeness scores. Alstonine demonstrated superior binding affinities against BCL-2 (–5.042 kcal/mol), PI3K (–6.017 kcal/mol), and STAT3 (–5.877 kcal/mol), comparable to known inhibitors such as Lisaftoclax and Napabucasin. Hydrogen bonding analysis revealed strong, short-range interactions (<2.0 Å) contributing to binding stability. Toxicity predictions classified both alkaloids as Class 3 (LD₅₀ = 215–300 mg/kg), indicating moderate toxicity that warrants optimization. ADME predictions revealed good oral bioavailability, high gastrointestinal absorption, and blood–brain barrier permeability.
Conclusion: Alstonine displayed the most promising anticancer potential, with favorable pharmacokinetic properties and multi-target binding profiles. These findings highlight the potential of Rauwolfia vomitoria alkaloids as lead scaffolds for anticancer drug development. Experimental validation and structural refinement are recommended to advance these compounds toward clinical applicability.
Keywords: Rauwolfia vomitoria, Ajmalicine, Alstonine, molecular docking, ADME, toxicity prediction, cancer therapeutics, indole alkaloids, computational pharmacology