Olatomide A. Fadare^1,, Ezekiel O.Iwalewa², Craig A. Obafemi¹, Feyisola P. Olatunji³

A well-known component of the Indian spice turmeric, curcumin, has received a lot of attention in recent years as a potential antimalarial agent but the inherent problems associated with low bioavailabilty tends to limit its applicability. The bioavailability is linked to its low solubility in water and its rapid break down in the blood plasma. In this study, we have proposed the use of synthetic analogs of curcumin and their derivatives which are expected to be less prone to degradation in the blood plasma as possible antimalarials. The binding affinity of monocarbonyl analogs of curcumin and their 2,4-dinitrophenylhydrazone derivatives for the chain A domain of plasmepsin II, one of the key enzymes involved in hemoglobin digestion in the food vacuole of the malaria parasite was determined by computational docking analysis, performed using Auto Dock Vina 1.1.2, pymol and Chem 3D ultra 12.0. The binding energies of the 20 compounds studied was compared with that of pepstatin A (a known inhibitor of plasmepsin II), curcumin and chloroquine. The 3D structure of the protein was obtained from the protein data bank (PDB ID:1M43), the compounds’ 3D structure was generated with the Chem 3D ultra 12.0 and visualization done with pymol. Out of the 20 compounds docked with plasmepsin II, 17 had binding energies higher than that of pep A (-32.6, kJ/mol) and 19 of the compounds had binding energies higher than that of curcumin (30.96, kJ/mol). The docked compounds, 5b, 6b and 7b had the highest binding energies (-44.73 kJ/mol, -42.64 kJ/mol and -41.80 kJ/mol respectively). It is expected that the compounds with binding energies higher than that of pep A may be considered for further antimalarial studies in-vitro and in-vivo.

monocarbonyl curcumin analog, 2, 4-dinitrophenyl hydrazone, low bioavailability, plasmepsin II, pepstatin A