Molecular modelling, synthesis, and antimalarial potentials of curcumin analogues containing heterocyclic ring

Abstract

The molecular modelling approach was applied to a series of nineteen curcumin analogues to find the possible PfRIO2 kinase inhibitory action. A putative active site in flexible loop (S1) of PfRIO2 kinase was explored computationally to recognize the molecular basis of ligands binding. The ligands (curcumin analogues; 3a–3s) were well accommodated in the selected active site (S1) due to their higher molecular size and length. Further all these synthesized compounds (3a–3s) were evaluated for their in vitro antimalarial activity according to the reported method. The antimalarial data showed that all these compounds to have parasiticidal activity with minimum killing concentrations (MKCs) range between 3.87 and 25.35 μM and schizonticidal activity with IC50 range between 1.48 and 23.09 μM. The compound 3p showed the most significant result with maximum schizonticidal (IC50; 1.48 ± 0.10 μM) and parasiticidal activities (MKC; 3.87 ± 0.36 μM) could be identified as promising lead for further investigations. Keywords: Antimalarial, Curcumin analogues, Kinase molecular modelling, Plasmodium falciparum, Pyrazole, Pyrimidine