Molecular Docking Studies of (2E)-1(1-Methyl-1H-Indol-3-yl)-3-Phenyl-Prop-2-en-one) as Antimalarial and Its Synthesis using Dimethylsulfate

Malaria is a disease with high prevalence in tropical and subtropical areas. The case of parasite resistance to proguanil, an antimalarial drug, has prompted the discovery of new drug candidates through molecular docking studies. In this study, we used the derivative of chalcone (2E)-1-(1-methyl-1H-indol-3-yl)-3-phenyl-prop-2-en-1-one as a test ligand and some comparison ligands to see its interaction with Plasmodium falciparum dihydrofolate reductase - thymidylate synthase ( Pf DHFR-TS) enzyme. Furthermore, the compound (2E)-1-(1-methyl-1H-indol-3-yl)-3-phenyl prop-2-en-1-one was synthesized by reacting (2E)-1-(1H-indol-3-yl)-3-phenyl prop-2-en-1-one and dimethyl sulfate through an N -alkylation reaction. The (2E)-1-(1-methyl-1H-indol-3-yl)-3-phenyl-prop-2-en-1-one has the higher Δ G bind (-7.53 kcal/mole) than native ligan WR99210(-8.83 kcal/mole), but has the lower than proguanil (-6.75 kcal/mole) and ( E )-3-(3,4-dimethoxy phenyl)-1-(2-hydroxy-4-methoxy-5-(prenyl)phenyl)-prop-2-en-1-one (-7.29 kcal/mole). However, there was only pi interaction of amino acid residue of the Pf DHFR-TS ligand complexes (PHE 58 , ILE 112 , LEU 119 , ALA 16 , ILE 14 ), in contrast to the WR99210 and proguanil complexes. This is similar to the interaction of the ( E )-3-(3,4-dimethoxyphenyl)-1-(2-hydroxy-4-methoxy-5-(prenyl)phenyl)-prop-2-en-1-one- Pf DHFR-TS complex which is active as an antimalarial in vitro , so that the test ligand still has a chance to be used as an antimalarial candidate. The compound (2E)-1-(1-methyl-1H-indol-3-yl)-3-phenyl prop-2-en-1-one was successfully synthesized with 41.55% yield.