title: Selected gold compounds cause pronounced inhibition of Falcipain 2 and effectively block P. falciparum growth in vitro.
abstract: A number of structurally diverse gold compounds were evaluated as possible inhibitors of Falcipain 2 (Fp2), a cysteine protease from P. falciparum that is a validated target for the development of novel antimalarial drugs. Remarkably, most tested compounds caused pronounced but reversible inhibition of Fp2 with K(i) values falling in the micromolar range. Enzyme inhibition is basically ascribed to gold binding to catalytic active site cysteine. The same gold compounds were then tested for their ability to inhibit P. falciparum growth in vitro; important parasite growth inhibition was indeed observed. However, careful analysis of the two sets of data failed to establish any direct correlation between enzyme inhibition and reduction of P. falciparum growth suggesting that Fp2 inhibition represents just one of the various mechanisms through which gold compounds effectively antagonize P. falciparum replication.
authors: Department of Medicinal Chemistry, University of Messina, Messina, Italy. nmicale@unime.it
authors: Nicola
authors: N
authors: Micale
authors: Maria Agostina
authors: MA
authors: Cinellu
authors: Laura
authors: L
authors: Maiore
authors: Anna Rosa
authors: AR
authors: Sannella
authors: Carlo
authors: C
authors: Severini
authors: Tanja
authors: T
authors: Schirmeister
authors: Chiara
authors: C
authors: Gabbiani
authors: Luigi
authors: L
authors: Messori
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D056831:Coordination Complexes / Q000494:pharmacology*; D046508:Culture Techniques; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006046:Gold; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development
chemical_list: D000962:Antimalarials; D056831:Coordination Complexes; D015853:Cysteine Proteinase Inhibitors; D006046:Gold; D003546:Cysteine Endopeptidases; C416224:falcipain 2