Identification and Characterization of Sesquiterpene Lactones as Potential Falcipain-2 Inhibitors

Abstract

Drug resistance affects the most effective anti-malarial medications, hence finding new, unique bioactive compounds with strong anti-malarial activity is extremely desirable. Falcipain-2 (2GHU) is a protease of plasmodium falciparum and considered as an important target to design antimalarial drugs. Objective: To identify potential novel falcipan-2 inhibitor for effect treatment of malaria. Methods: Molecular docking analysis was performed by using different bioinformatic tools to check the interaction between the Alantolactone and Brevilin A and falcipain-2 (2GHU). Results: Alantolactone and Brevilin A show a strong affinity to bind with 2GHU with binding energy values -7.2kcal/mol and -8.1kcal/mol respectively. Moreover, results of ADMET and cytotoxicity analysis showed that both investigated compounds strongly followed the Lipinski rule of five for drug-likeness and are quite safe to be used as an antimalarial drug. Conclusions: Both of the studied sesquiterpene lactones may inhibit falcipain-2, according to the results of our molecular docking study, but Brevilin A is predicted to be the most effective inhibitor because it forms strong hydrogen bonds with the protein's amino acid residues and has lower values for binding energy and inhibition constant. Therefore, new anti-malarial medications can be created from these two bioactive sesquiterpene lactone molecules to overcome the resistance of plasmodium falciparum against already clinically approved drugs.