title: Inhibition of P. falciparum PFATP6 by curcumin and its derivatives: a bioinformatic study.
abstract: Curcumin, a yellow spice has been shown to have many pathological uses including cancer and malaria. Recent experimental data have shown the inhibitory effect of curcumin and its two derivatives on the growth of Plasmodium falciparum in cell culture at low micromolar concentrations. Previous studies have suggested that Ca(2+)—ATPase (PfATP6) of P. falciparum is the target of many antimalarial drugs. However, the mechanism of inhibition of Ca(2+)—ATPase (PfATP6) is not known. In addition, it is not clear which specific isomeric form of curcumin is the most potent inhibitor of P. falciparum. Here we address this issue using bioinformatics tools. We generated a molecular model of Ca(2+)—ATPase (PfATP6) of P. falciparum and carried out molecular docking of all curcumin analogues of Zinc database of compounds (zinc.docking.org). Two molecular docking programs Glide and FlexX were used to determine binding feasibility of 351 analogues of curcumin. The comparison of docking parameters showed, more than 20 analogues are better ligands of PfATP6 than curcumin itself. . The binding of curcumin and its analogues to PFATP6 is mediated by both hydrophobic and polar interactions. Our results suggest that curcumin analogues are promising lead compounds for the development of antimalarial drugs.
authors.affiliation: Department of Chemistry, K. S. Saket P. G. College, Ayodhya, Faizabad- 224001, India.
authors.forename: A
authors.initials: A
authors.lastname: Shukla
authors.forename: A
authors.initials: A
authors.lastname: Singh
authors.forename: A
authors.initials: A
authors.lastname: Singh
authors.forename: L P
authors.initials: LP
authors.lastname: Pathak
authors.forename: N
authors.initials: N
authors.lastname: Shrivastava
authors.forename: P K
authors.initials: PK
authors.lastname: Tripathi
authors.forename: M P
authors.initials: MP
authors.lastname: Singh
authors.forename: K
authors.initials: K
authors.lastname: Singh
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D019295:Computational Biology / Q000379:methods*; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000935:Antifungal Agents; D003474:Curcumin