Hypervalent organotellurium compounds as inhibitors of P. falciparum calcium-dependent cysteine proteases

Hypervalent organotellurium compounds as inhibitors of P. falciparum calcium-dependent cysteine proteases

Author Maluf, Sarah El Chamy Autor UNIFESP Google Scholar
Melo, Pollyana M. S. Autor UNIFESP Google Scholar
Varotti, Fernando P. Google Scholar
Gazarini, Marcos L. Autor UNIFESP Google Scholar
Cunha, Rodrigo L. O. R. Google Scholar
Carmona, Adriana K. Autor UNIFESP Google Scholar
Abstract Hypervalent organotellurium compounds (organotelluranes) have shown several promising applications, including their use as potent and selective cysteine protease inhibitors and antiprotozoal agents. Here, we report the antimalarial activities of three organotellurane derivatives (RF05, RF07 and RF19) in two Plasmodium falciparum strains (CQ(s) 3D7 and CQ(R) W2), which demonstrated significant decreases in parasitemia in vitro. The inhibition of intracellular P. falciparum proteases by RF05, RF07 and RF19 was determined and the IC50 values were 3.7 +/- 1.0 mu M, 1.1 +/- 02 mu M and 02 +/- 0.01 mu M, respectively. Using an assay performed in the presence of the ER Ca2+-ATPase inhibitor we showed that the main enzymatic targets were cysteine proteases stimulated by calcium (calpains). None of the compounds tested caused haemolysis or a significant decrease in endothelial cell viability in the concentration range used for the inhibition assay. Taken together, the results suggest promising compounds for the development of antimalarial drugs. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Keywords Plasmodium
Malaria
Calpain
Tellurium compounds
xmlui.dri2xhtml.METS-1.0.item-coverage Clare
Language English
Date 2016
Published in Parasitology International. Clare, v. 65, n. 1, p. 20-22, 2016.
ISSN 1383-5769 (Sherpa/Romeo, impact factor)
Publisher Elsevier Ireland Ltd
Extent 20-22
Origin https://doi.org/10.1016/j.parint.2015.09.006
Access rights Closed access
Type Article
Web of Science ID WOS:000366228500004
URI https://repositorio.unifesp.br/handle/11600/58533

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