Determination of effective Plasmodium falciparum dihydropteroate synthase inhibitors using molecular docking technique

Abstract

Nowadays, malaria is still a serious global health problem. The most severe form is caused by Plasmodium falciparum parasites. Dihydropteroate synthase enzyme (DHPS) plays an important role in genetics material synthesis of P.falciparum parasites. Nonetheless, an effective inhibitor of P.falciparum DHPS is currently not available due to drug resistance of the parasites. Therefore, the objective of the research is to determine the potent inhibitors of P. falciparum DHPS using molecular docking technique. Totally 19 putative inhibitors were docked to the DHPS wild-type and four mutants. Results showed high possibility that the sulfa inhibitors, SDX-DHP and STZ-DHP, are inactive with the mutant enzymes due to the absence of the interaction with residue PRO 438. Since the interaction with this amino acid could be found in the inhibitor PTA binding with any types of enzymes while the interaction with sulfa drugs only occurs in the wild-type class. According to our docking results, 7,8-dihydropteroic acid (ligand number 14) is the ligand with a fair potential to be active with the mutants as certain amino acid interactions similar to the inhibitor PTA were found. Moreover, ligand 14 might possibly be active with every enzyme due to the interaction with the key amino acid residues LYS 609 and ARG 686.