In Silico Docking and ADME-Tox evaluation of annonacin : Addressing contradictions in antimalarial evidence against PfDHODH and PfLDH

Authors

Published 2025-12-08
Issue Vol. 16 No. 2 (2025): December 2025
Section Original Research Articles
DOI: https://doi.org/10.30659/sainsmed.v16i2.39412
Keywords: Annonacin, Antimalarial, Molecular Docking, PfDHODH, PfLDH, Toxicity

Abstract

The rise of resistance to current antimalarial therapies highlights the urgent need for novel drug candidates.
Annona muricata contains phenolic compounds, particularly annonaceous acetogenins, known for their
bioactive properties and cytotoxicity. This study investigates the binding affinity of Annonacin to the
malaria target proteins PfDHODH and PfLDH and assesses its toxicity and pharmacokinetic properties
using in silico methods. Molecular docking was performed using Molegro Virtual Docker (MVD) version
6.0 to explore Annonacin’s binding interactions with PfDHODH and PfLDH. Toxicity was evaluated
using ProTox-II, focusing on cytotoxicity and LD50 values. Pharmacokinetic parameters, including
gastrointestinal absorption and compliance with Lipinski’s Rule of Five, were analysed using SwissADME.
Docking analyses indicated stable complexes of Annonacin with both PfDHODH and PfLDH, suggesting
strong inhibitory potential. Toxicity evaluation revealed significant cytotoxic effects, with an LD50 of
400 mg/kg, placing Annonacin in Toxicity Class IV, indicating risk upon ingestion. Pharmacokinetic
assessments identified challenges, including low gastrointestinal absorption and a violation of Lipinski’s
rule due to Annonacin’s high molecular weight. Annonacin demonstrates notable antimalarial potential;
however, its development is limited by safety issues and pharmacokinetic constraints. Optimisation efforts
are essential to enhance efficacy and safety, laying the groundwork for future research and development.

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© 2025 Author(s). Published by Sains Medika: Jurnal Kedokteran dan Kesehatan. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

How to Cite

Tsaqif, A. Z., Khodijah, K., Prayogi, F. R., Nuryady, M. M., & Ariesaka, K. M. (2025). In Silico Docking and ADME-Tox evaluation of annonacin : Addressing contradictions in antimalarial evidence against PfDHODH and PfLDH. Sains Medika: Jurnal Kedokteran Dan Kesehatan, 16(2), 56-64. https://doi.org/10.30659/sainsmed.v16i2.39412

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