Maulana Yusuf Alkandahri , Recky Patala , Afiat Berbudi , Anas Subarnas

Abstract

Malaria is a major global health problem caused by plasmodium parasites. The alarming spread of drug resistance and its limited availability underscores the importance of discovering new antimalarial compounds. This study aims to examine the interaction of curcumin and kaempferol on the triose-phosphate isomerase receptor of P. falciparum strain through an in-silico trial using a structure-based drug design method. Molecular docking was performed using crystalline protein triose-phosphate isomerase (PDB ID: 1O5X) from P. falciparum TIM complexed into 2-phosphoglycerate from protein database (https://www.rcsb.org/). Furthermore, curcumin and kaempferol compounds have better free energy binding values, which are -8.57 and -9.02 kcal/mol compared to 2-phosphoglycerate which is -5.97 kcal/mol. Considering the value of the inhibition constant, curcumin and kaempferol compounds also had a lower value of 0.523 and 0.244 µM, compared to 2-phosphoglycerate, which was 41,970 µM. In addition, curcumin compounds have five interactions with 2-phosphoglycerate, one of which is a hydrogen bonding interaction on the amino acid GLY171 and it interacts with the hydroxy group on the structure of curcumin. Kaempferol compounds have six interactions with 2-phosphoglycerate, two of which are hydrogen bonding interactions including amino acids GLY232 and VAL212 which interact with the hydroxy group on the structure. These two compounds have antimalarial activity through competitive inhibition of 2-phosphoglycerate against triose-phosphate isomerase receptors. They are also better than 2-phosphoglycerate when assessed from the results of hydrogen bonding interaction, inhibition constants, and types of amino acid interactions obtained from the in-silico trial using the structure-based drug design method‎.

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