AccScience Publishing / MI / Online First / DOI: 10.36922/MI025370100
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ORIGINAL RESEARCH ARTICLE

In silico docking and pharmacokinetic evaluation of African ethnomedicinal phytochemicals as dual-target inhibitors of multidrug-resistant Gram-negative bacteria

Kanayo Samuel Okonji1* ,  Prachi Dash2
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1 Department of Chemistry, Faculty of Science, Federal University Otuoke, Yenagoa, Bayelsa State, Nigeria
2 Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Chennai, Tamil Nadu, India
MI, 025370100 https://doi.org/10.36922/MI025370100
Received: 9 September 2025 | Revised: 28 October 2025 | Accepted: 4 November 2025 | Published online: 24 November 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

The emergence of multidrug-resistant (MDR) Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa, poses a critical global health challenge, necessitating innovative antimicrobial strategies. Leveraging Africa’s rich phytochemical diversity, this study integrates molecular docking and in silico pharmacokinetic profiling to identify natural compounds with dual-target potential. Ten bioactive phytochemicals from ethnomedicinal plants were screened against four validated bacterial targets: LasR (2UV0), AcrB efflux pump (5NC5), DNA gyrase B (6F86), and TEM-1 β-lactamase (1BTL) with AutoDock Vina implemented in PyRx, and the resulting protein–ligand interactions analyzed in Discovery Studio. Docking identified luteolin as exhibiting the highest binding affinity for LasR (−10.8 kcal/mol) and TEM-1, indicating dual inhibition of quorum sensing and β-lactamase activity. Rutin (−9.2 kcal/mol) exhibited high affinity for AcrB, indicating potential efflux pump inhibition, while ellagic acid (−8.3 kcal/mol) targeted DNA gyrase, potentially impairing bacterial replication. Absorption, distribution, metabolism, excretion, and toxicity analyses, along with ProTox-3 predictions, indicated that luteolin exhibited high gastrointestinal absorption and moderate systemic toxicity. Ellagic acid exhibited excellent biocompatibility, whereas rutin showed favorable drug-likeness but low permeability. Collectively, luteolin, rutin, and ellagic acid emerged as promising computational leads with complementary inhibitory mechanisms. This study highlights the translational potential of African phytochemical scaffolds in rational, computer-aided antimicrobial design and provides a foundation for subsequent in vitro and in vivo validation toward novel anti–MDR therapeutics.

Graphical abstract
Keywords
Luteolin
Rutin
Ellagic acid
Multidrug resistance
Gram-negative bacteria
Molecular docking
ADMET
African medicinal plants
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Microbes & Immunity, Electronic ISSN: 3029-2883 Print ISSN: 3041-0886, Published by AccScience Publishing
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