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In Silico Exploration of the Antimicrobial Potential of Diospyros-Derived Bioactives Against Acinetobacter baumannii

Soundaryalakshmi Ramesh, Priyanga Paranthaman, Shanthi Veerappapillai, Ramanathan Karuppasamy

Abstract


Antimicrobial Resistance (AMR) is a major health threat in the 21st century, driven by the growing number of resistant infections and the lack of new antibiotics. Without effective measures, AMR could become the leading cause of death by 2050. Among the WHO-identified ESKAPE pathogens, Acinetobacter baumannii is of particular concern due to its ability to evade antibiotic treatment. Notably, carbapenem-resistant A. baumannii (CRAB), driven mainly by overexpression of OXA-23 class D β-lactamase, is associated with prolonged hospital stays and high mortality, making it a top priority for antibiotic research. The lack of effective treatments also increases risks in surgery and chemotherapy. These challenges highlight the need for alternative strategies, with phytochemicals recently gaining attention as promising candidates for combating AMR. Accordingly, a combination of computational pipelines and emerging machine learning–based algorithms was applied to perform a structured investigation of phytochemicals with antibacterial potential. Therefore, this study investigates the potential of the genus Diospyros against CRAB, where a total of 448 compounds were retrieved from the Indian Medicinal Plants, Phytochemistry and Therapeutics 2.0 (IMPPAT 2.0) database, of which 135 unique molecules were docked against OXA-23. Machine learning–based scoring refined the results to 20 leads, and ADMET analysis identified Diosindigo B as the most promising candidate with favorable pharmacokinetics, drug-likeness, and low toxicity. The compound was further analyzed using interaction studies, scaffold analysis, and molecular dynamics (MD) simulations. Overall, Diosindigo B shows potential as a therapeutic candidate against CRAB; however, experimental validation is required to confirm its efficacy.

Keywords



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