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Volume 24, Issue 3
  • ISSN: 1871-529X
  • E-ISSN: 2212-4063

Abstract

Introduction

The 70 kDa heat shock proteins (Hsp70) are ubiquitous molecules that play central roles in protein homeostasis. Their nucleotide-binding domains (NBD) are associated with the J domains of 40 kDa co-chaperone ‘HSP40’ in performing their functions. Interruption of this interaction significantly impacts the critical ATPase activity of Hsp70s, making them dysfunctional.

Methods

MAL2-11B is a dihydropyrimidine derivative that blocks Hsp70-Hsp40 interaction and hence holds the potential to be used as a drug. This Hsp70 inhibitor is a structural analogue of MAL3-101 that has proven anti-cancer and antiparasitic activity. MAL2-11B is predicted to have better drug-likeness, solubility, and absorption properties than MAL3-101. In the present study, we have therefore explored the potential of MAL2-11B as an antimalarial by using tools.

Results

Molecular docking of MAL2-11B with all Hsp70 (PfHsp70) proteins revealed its preferential affinity for two out of four homologs at the nucleotide-binding site. Detailed analysis of the docked complexes helped us to predict the kind of protein-inhibitor interactions and specific amino acid residues involved in binding.

Conclusion

After validation, these data may be used as the groundwork for the design and development of new inhibitors and drugs against malaria.

© 2024 Bentham Science Publishers
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2024-08-23
2025-01-19

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Understanding Interactions between a Potential Antimalarial ‘MAL2-11B’ and its Targets using In Silico Methods
Cardiovasc Hematol Disord Drug Targets 24, 151 (2024); https://doi.org/10.2174/011871529X309936240821072630
/content/journals/chddt/10.2174/011871529X309936240821072630
/content/journals/chddt/10.2174/011871529X309936240821072630
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  • Article Type:     Research Article
Keyword(s): heat shock proteins; Malaria; molecular docking; nucleotide binding domain; Plasmodium falciparum; substrate binding domain

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