Molecular Docking Analysis of Pyrimethamine Derivatives with Plasmodium falciparum Dihydrofolate Reductase

Abstract

DHFR from Pf is a known target for malaria. There is a continued effort for the design and development of the potent inhibitor for PfDHFR in the control of malaria. Therefore it is of interest to screen PfDHFR with the derivatives of Pyrimethamine. The results show that the compound CID 10476801 has lowest docked energy (-11.48 kcal/mol) with protein likely to be a drug candidate, probably inhibiting PfDHFR structure. Residues of PfDHFR protein involved in the formation of hydrogen bonds with compound CID 10476801 are confirmed to be ASP54. The findings provide new insights into development of potent chemotherapeutic drug for combating malaria.

Keywords: Analogues; Antifolate; Antimalarial; DHFR; Plasmodium falciparum; de novo; inhibitors; quadruple mutant; resistance; validated targets.

Figure 1

Molecular Interaction of ligand with native enzyme protein PfDHFR using Autodock.

Figure 2

Docked complex showing the interaction between PfDHFR and the inhibitor compound (CID 10476801). Dotted yellow lines indicate the hydrogen bonding between amino acid residue ASP54 and the compound CID: 10476801.