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Lead Selection of Antiparasitic Compounds from a Focused Library of Benzenesulfonyl Derivatives of Heterocycles
1 , 2 , 2 , * 3 , 1
1  Universidad Nacional de Córdoba
2  Swiss Tropical and Public Health Institute
3  Southern Illinois University Edwardsville

Published: 01 November 2016 by MDPI in 2nd International Electronic Conference on Medicinal Chemistry session ECMC-2

A library of 69 synthetic benzenesulfonyl derivatives of heterocycles, with drug-like properties, was assayed for in vitro antiparasitic activity and the results were added to our previous reports for a comprehensive SAR discussion. Seven compounds showed an IC50 between 0.25-3μM against L. donovani and low cytotoxicity. Compound 1-(2,3,5,6-tetramethylphenylsulfonyl)-2-methylindoline (G16), was particularly interesting with an IC50 similar to the reference drug miltefosine. In addition, seven compounds showed an IC50 below 6µM against T. cruzi, and three of them (E3, E9 and G3) were identified as lead scaffolds for further optimization based on their activity-toxicity profile. Furthermore, two promising structures (B15 and G15) have shown moderate inhibitory activity against P. falciparum. In general, the presence of a benzenesulfonyl moiety improves the antiparasitic activity of the heterocycles included in this study (with exception of T. b. rhodesiense) validating the criteria used in the selection of the fragment-based drug design approach. Finally, from the SAR analysis it could be concluded that the presence of electron withdrawing and lipophilic groups were favorable for the antiparasitic activity.

Keywords: antiparasitic activity, benzenesulfonyl, heterocycles, SAR, library compounds.