A new class of
copper(II) nanohybrid solids, LCu(CH(3)
COO)(2) and LCuCl(2), have been synthesized and characterized by transmission electron microscopy, dynamic light scattering, and IR spectroscopy, and have been found to be capped by a
bis(benzimidazole)
diamide ligand (L). The particle sizes of these nanohybrid solids were found to be in the ranges 5-10 and 60-70 nm, respectively. These nanohybrid solids were evaluated for their in vitro
antimalarial activity against a
chloroquine-sensitive isolate of Plasmodium falciparum (MRC 2). The interactions between these nanohybrid solids and
plasmepsin II (an aspartic
protease and a plausible novel target for
antimalarial drug development), which is believed to be essential for
hemoglobin degradation by the parasite, have been assayed by UV-vis spectroscopy and inhibition kinetics using Lineweaver-Burk plots. Our results suggest that these two compounds have
antimalarial activities, and the IC(50) values (0.025-0.032 microg/ml) are similar to the IC(50) value of the standard
drug chloroquine used in the bioassay. Lineweaver-Burk plots for inhibition of
plasmepsin II by LCu(CH(3)
COO)(2) and LCuCl(2) show that the inhibition is competitive with respect to the substrate. The inhibition constants of LCu(CH(3)
COO)(2) and LCuCl(2) were found to be 10 and 13 microM, respectively. The IC(50) values for inhibition of
plasmepsin II by LCu(CH(3)
COO)(2) and LCuCl(2) were found to be 14 and 17 microM, respectively.
Copper(II)
metal capped by a
benzimidazole group, which resembles the
histidine group of
copper proteins (
galactose oxidase, beta-
hydroxylase), could provide a suitable anchoring site on the nanosurface and thus could be useful for inhibition of target
enzymes via binding to the S1/S3 pocket of the
enzyme hydrophobically. Both
copper(II) nanohybrid solids were found to be nontoxic against human
hepatocellular carcinoma cells and were highly selective for
plasmepsin II versus human
cathepsin D. The pivotal mechanism of
antimalarial activity of these compounds via
plasmepsin II inhibition in the P.
falciparum malaria parasite is demonstrated.