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This study evaluates harmicine derivatives for their ability to inhibit falcipain-2 in Plasmodium falciparum.

May 19, 2026Open Access

Molecular Docking, Dynamics Simulation and ADMET Prediction of Harmicine Derivatives as Plasmodial Falcipain-2 Inhibitors

MGMuh. Arfandy GunawanMaterials Research Group (United States)HRHerlina RasyidHasanuddin University AAAsmawati AsmawatiHasanuddin University

Key Points

This study evaluates harmicine derivatives for their ability to inhibit falcipain-2 in Plasmodium falciparum.
Molecular docking was employed to assess binding interactions with falcipain-2.
Dynamics simulation was conducted for 100 nanoseconds to test stability of compound 6f.
ADMET prediction was used to analyze the pharmacokinetic properties of harmicine derivatives.
Compound 6f demonstrated a binding affinity score of -8.4, greater than chloroquine's -5.5.
Compound 6f remained stable at the binding site for 100 ns during dynamics simulation.
The compound successfully passed Lipinski's Rule of Five, indicating potential for oral administration.

Abstract

Currently, the rise and dissemination of resistance to antimalarial drugs pose a significant global challenge. There is an ongoing effort to discover novel compounds for the development of new antimalarial therapies. This study aimed to evaluate harmicine derivatives known for their antimalarial activity and to explore their potential interactions with Plasmodium falciparum, specifically targeting the crucial falcipain-2 enzyme in the parasite's life cycle. Molecular docking and dynamics studies showed that compound 6f interacted with the binding site of the enzyme and stayed stable for 100 ns, the best of the derivatives. It had a binding affinity score of -8.4, higher than chloroquine (-5.5). This means that it might be better than chloroquine at inhibiting falcipain-2. Additionally, compound 6f successfully passed Lipinski's Rule of Five, suggesting its potential for oral use. Researchers found that the results of this study could help make new, stronger Harmicines with better antiplasmodial activities. This could lead to the creation of very effective medicines that fight malaria

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