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

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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