Taye Alawode

In Silico Evaluation of Phytochemicals from Icacina Trichantha as Potential Anti-Tuberculosis Agents

Introduction

In silico evaluation of phytochemicals from icacina trichantha as potential anti-tuberculosis agents. In silico study evaluates Icacina trichantha phytochemicals as potential anti-tuberculosis agents. Molecular docking identifies promising compounds with superior binding, drug-likeness & low toxicity.

Abstract

The emergence of drug-resistant strains of Mycobacterium tuberculosis and the limitations of current therapies has necessitated a search for more effective drugs for tuberculosis. This study investigates phytoconstituents from the Icacina trichantha tubers as potential anti- tuberculosis agents. A molecular docking approach, employing SwissDock, was used to evaluate the interactions of twenty (20) phytoconstituents with key M. tuberculosis proteins, including DprE1 (6HEZ), InhA (1ENY), KasA (2WGE), PanK type 1 (4BFT), PknB (2FUM), and Pks13 (5V3X). Furthermore, the compounds were screened for drug-likeness and toxicity using SwissADME and admetSAR, respectively. The results revealed that most phytochemicals exhibited superior binding affinities compared to standard anti-tuberculosis drugs. Icaceine, humirantholide C, icacinlactone G, 17-hydroxyicacinol, and hydroxyicacinlactone B were identified as the most promising candidates based on their binding energies. Drug-likeness evaluations confirmed that all the compounds met Lipinski’s criteria. Toxicological analysis (using admetSAR) revealed that the compounds were non-carcinogenic, non-AMES toxic, and weak HERG channel inhibitors, however, in vitro and in vivo assessments are needed to validate these findings. This study highlights the potential of phytochemicals in tubers of Icacina trichantha as promising leads for anti-tuberculosis drug development.

Review

This study presents a compelling in silico investigation into the potential anti-tuberculosis activity of phytochemicals derived from *Icacina trichantha* tubers. Addressing the critical need for novel therapeutics against drug-resistant *Mycobacterium tuberculosis*, the authors employed a comprehensive computational approach. Their methodology involved molecular docking of twenty phytoconstituents against six key *M. tuberculosis* proteins, alongside evaluations of drug-likeness and toxicity using established platforms like SwissADME and admetSAR. The study's strength lies in its systematic screening, which identified several promising compounds exhibiting superior binding affinities compared to standard anti-TB drugs, marking a significant first step in drug lead identification. The results highlight Icaceine, humirantholide C, icacinlactone G, 17-hydroxyicacinol, and hydroxyicacinlactone B as particularly promising candidates, based on their favorable binding energies across multiple protein targets. Crucially, the compounds also demonstrated good drug-likeness according to Lipinski’s rules and exhibited favorable preliminary toxicity profiles, being largely non-carcinogenic and non-AMES toxic. This combination of strong binding affinity to essential bacterial targets and acceptable pharmacokinetic/toxicological properties in silico positions these phytochemicals as excellent starting points for further development in the challenging field of anti-tuberculosis drug discovery. While the in silico findings are highly encouraging and effectively establish a strong rationale for further investigation, it is imperative to acknowledge the inherent limitations of computational studies. The authors themselves appropriately point out the critical need for experimental validation. Therefore, the immediate next steps for this research should involve rigorous *in vitro* assays to confirm the observed binding affinities and evaluate the antimicrobial efficacy of these identified compounds against *M. tuberculosis*. Subsequent *in vivo* studies will then be essential to assess their therapeutic potential and safety within biological systems. Despite being a preliminary computational study, this work makes a valuable contribution by pinpointing novel chemical scaffolds from a natural source that warrant dedicated experimental follow-up in the quest for new anti-tubercular agents.

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