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Vol. 36 No. 10 (2024): Vol 36 Issue 10, 2024

Copyright (c) 2024 Siti Zafirah Zulkifli, Ahmad Amzar Abdul Aziz, Aimi Suhaily Saaidin, Nuraisyikin Hamzah, Noor Hidayah Pungot

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Molecular Docking and ADME Profiles of Hyrtiosulawesine Derivatives Targeting pfLDH: Exploring Potential as Antimalarial Agents

https://doi.org/10.14233/ajchem.2024.32318
Siti Zafirah Zulkifli
Organic Synthesis Laboratory, Institute of Science (IOS), Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Sciences, Universiti Teknologi MARA, 40450, Shah Alam, Selangor, Malaysia
https://orcid.org/0000-0003-2530-8194
Ahmad Amzar Abdul Aziz
Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia (IIUM) 25200 Kuantan, Pahang, Malaysia
Aimi Suhaily Saaidin
Organic Synthesis Laboratory, Institute of Science (IOS), Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia
https://orcid.org/0000-0002-7968-6169
Nurasyikin Hamzah
Department of Chemistry, Kulliyyah of Science, International Islamic University Malaysia (IIUM) 25200 Kuantan, Pahang, Malaysia
https://orcid.org/0000-0002-5115-227X
Noor Hidayah Pungot
Organic Synthesis Laboratory, Institute of Science (IOS), Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor, Malaysia; Faculty of Applied Sciences, Universiti Teknologi MARA, 40450, Shah Alam, Selangor, Malaysia
https://orcid.org/0000-0003-0322-263X

Corresponding Author(s) : Noor Hidayah Pungot

noorhidayah977@uitm.edu.my

Asian Journal of Chemistry, Vol. 36 No. 10 (2024): Vol 36 Issue 10, 2024

Abstract

The relentless rise in Plasmodium falciparum’s resistance to existing antimalarial drugs has sparked an urgent quest for novel therapeutic agents. For centuries, natural resources have been the bedrock of medicinal remedies, with β-carboline emerging as a beacon of hope in antimalarial research. In this study, we delve into the potential of hyrtiosulawesine derivatives as revolutionary antimalarial compounds, utilizing hyrtiosulawesine as the crucial scaffold. Employing a sophisticated amalgamation of molecular docking and ADME (absorption, distribution, metabolism and excretion) profiling, we meticulously screened an extensive library of hyrtiosulawesine’s derivatives against P. falciparum. Based on advanced computational techniques, the binding affinities and interaction profiles were assessed and culminating in the selection of the most promising candidates based on their exceptional binding interactions. Moreover, the comprehensive ADME analyses were performed to assess the pharmacokinetic properties of these derivatives, ensuring their suitability as drug candidates. The results showed that most of the analogues exhibited strong binding affinities (-7.2 to -9.8 kcal/mol) to the Plasmodium falciparum lactate dehydrogenase (pfLDH) protein, surpassing that of hyrtiosulawesine itself. Among these, compounds 2t and 1w demonstrated the strongest binding, likely due to hydrogen bonding with Arg171 and Asn197. ADME profiling revealed that all hyrtiosulawesine derivatives displayed favourable drug-likeness properties and adhered to the Lipinski Rule of 5 (Ro5) indicating their potential efficacy as antimalarial agents. This investigation provides a foundation for further in vitro and in vivo investigations paving the way for the development of effective treatments against malaria.

Keywords

ADME Antimalarial Hyrtiosulawesine analogues Molecular docking
Zulkifli, S. Z., Abdul Aziz, A. A., Saaidin, A. S., Hamzah, N., & Pungot, N. H. (2024). Molecular Docking and ADME Profiles of Hyrtiosulawesine Derivatives Targeting pfLDH: Exploring Potential as Antimalarial Agents. Asian Journal of Chemistry, 36(10), 2475–2484. https://doi.org/10.14233/ajchem.2024.32318
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