Design, Synthesis and Molecular Modeling Studies of Thiosemicarbazone & Thiazole Derivatives as Potential Anti-Malarial Agents
Abstract A series of novel thiosemicarbazone & thiazole derivatives (Kp1-10) have been designed, synthesized and evaluated for potential anti-malarial activity. The antimalarial activity of the synthesized thiazole derivatives (Kp1-10) was assessed against human pathogenic malarial strain viz. Plasmodium falciparum while quinine was taken as the standard drug. compound Kp-9 was found to be most promising which exhibited strongest inhibitory activity against P. falciparumwith an IC50 value of 0.29µg/mL which was higher than the reference drug quinine (1.26µg/mL). The SAR studyrevealed that thesubstitution with electron withdrawing group at phenyl increases anti-malarial activity as shown in compound Kp-9. The result of molecular docking studies showed that compounds Kp-9, Kp-1, Kp-3, Kp-4 showed good docking scores with protein (PDB code: 5TBO). The compound Kp-9 showed highest docking score (-9.519). Whereas, compounds Kp-1, Kp-3, Kp-4 and Kp-10 showed good docking scores (-8.764, -8.406, -9.062, -9.435 respectively) with critical interactions with the amino acid residues such as VAL532, ILE237, LEU531, HIE185, TYR528, ASN274, ARG265. The results of biological activity and docking study revealed that the presence of electron withdrawing group at 4th position of phenyl ring attached is crucial for better anti-malarial activity and favorable drug-like profile which can emerge as a potential drug molecule in further development.