Selected gold compounds cause pronounced inhibition of Falcipain 2 and effectively block P. falciparum growth in vitro |
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| Authors: | Micale Nicola Cinellu Maria Agostina Maiore Laura Sannella Anna Rosa Severini Carlo Schirmeister Tanja Gabbiani Chiara Messori Luigi |
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| Affiliation: | a Department of Medicinal Chemistry, University of Messina, Messina, Italyb Department of Chemistry, University of Sassari, Sassari, Italyc Department of Infectious, Parasitic and Immunomediated Diseases, Vector-Borne Diseases and International Health Section, Istituto Superiore di Sanità, Rome, Italyd Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Wuerzburg, Germanye Department of Chemistry, University of Florence, Florence, Italy |
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| 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 Ki 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. |
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| Keywords: | Gold compounds Metallodrugs Malaria Falcipain 2 |
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