SYNTHESIS AND MOLECULAR DOCKING STUDY OF 2-ARYL/HETEROARYL-6-CHLOROQUINOLINE-4-CARBOXYLIC ACIDS WITH PLASMODIUM LDH RECEPTOR PROTEIN
Keywords:Pfitzinger synthesis, 2-arylheteroaryl-quinoline-4-carboxylic acids, Molecular docking, Lactate dehydrogenase (LDH), Antimalarial
Objective: Synthesis and in silico molecular docking studies of 2-aryl/heteroaryl-quinoline-4-carboxylic acid derivatives (3a-j) with plasmodium LDH receptor protein.
Methods: The 2-aryl/heteroaryl-quinoline-4-carboxylic acids (3a-j) were obtained by Pfitzinger reaction. Ligands (3a-j) interaction with plasmodium LDH receptor protein was studied through molecular docking method.
Results: Good yields of 2-aryl/heteroaryl-quinoline-4-carboxylic acid derivatives (3a-j) were obtained by convenient and economical procedure. Their structures were confirmed by 1H NMR, 13C NMR, and MS spectral analysis. The binding site analysis of the synthesized compounds (3a-j) with plasmodium LDH receptor that are responsible for malaria parasite response was evaluated through molecular docking study. The results reveal that the ligand 3d shows maximum of five hydrogen bonding interactions with binding energy -9.05 kcal/mol, shown to be a promising lead molecule to inhibit Plasmodium LDH receptor.
Conclusion: The docking studies of newly synthesized 2-aryl/heteroaryl-quinoline-4-carboxylic acids were found to be very useful ligands for antimalarial therapy particularly on Plasmodium LDH protein. However the installation of still many appropriate substitutions on quinoline moiety would lead to identification of novel antimalarial compounds that ascertained via molecular docking is underway in our lab.
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