Antiparasitic and cytotoxicity assays of benzenesulfonyl derivatives of heterocycles against Trypanosoma cruzi

MIANA GE; SANCHEZ-MORENO, M; MAZZIERI MR

Otro; III Reunión Internacional de Ciencias Farmacéuticas ? RICiFa 2014; 2014

UNC y UNR

A chemical focused library of benzenesulfonyl derivatives of heterocycles, BSHet, was designed and synthetized in our laboratories. Preliminary screening of some of them showed interesting activity against protozoarian parasites.1,2,4 At present, 146 compounds with drug-like molecular properties were included in the library1-3. Because of the need of new antiparasitic agents against Chagas disease, the aim of this work was to carry out a careful screening on in vitro activity against epimastigotes of Trypanosoma cruzi (Tc) and on cytotoxicity. The BSHet were synthesised by methods previously reported.1-4 Currently, 116 derivatives were screened by method described by Sánchez Moreno et al.5 Epimastigotes Tc (cultured in vitro in MTL medium plus 10% inactivated foetal bovine serum medium) were incubated with the BSHet at 1, 10, 25 and 50 µM. The number of epimastigotes was determined at 72 h. by using a Neubauer hemocytometric chamber in triplicate. The unspecific cytotoxicity assays were performed against Vero cells (cultured in RPMI medium plus 10% inactivated foetal bovine serum medium) incubated with the BSHet at same concentrations. After 72 h., the cell viability was determined by flow cytometry. Both determinations were expressed as IC50 and determined in comparison to the control culture. Besides, the selectivity index, SI, was calculated as the ratio between cytotoxicity and activity index. Results showed 19 derivatives with SI lower than benznidazole (reference compound) and qualified6 to enter to the next step, the in vitro screening against amastigotes and trypomastigotes forms. The screening of 116 derivatives of a focused in house library of BSHet showed high in vitro activity against epimastigotes Tc and low cytotoxicity over Vero cells. 19 out of 116 compounds could be selected as hits7 and also will be screened over amastigotes and trypomastigotes forms, the infective forms at the human host.