Lead selection of antiparasitic compounds from a focused library of benzenesulfonyl derivatives of heterocycles

PAGLIERO, R; KAISER; R. BRUN; M. J. NIETO; M. R. MAZZIERI

BIORGANIC AND MEDICINAL CHEMISTRY LETTERS

Essevier

Año: 2017 vol. 27 p. 3945 - 3945

0960-894X

library of 89 synthetic benzenesulfonyl derivatives of heterocycles with drug-like properties wasassayed for in vitro antiparasitic activity and the results were added to our previously reported derivativesfor a comprehensive SAR evaluation. Four compounds showed an IC50 between 0.25 and 3 lMagainst Leishmania donovani and low cytotoxicity. Compound G{16} (1-(2,3,5,6-tetramethylphenylsulfonyl)-2-methylindoline), was particularly interesting with an IC50 similar to the reference drug miltefosine.Seven compounds showed an IC50 below 6 mM against Trypanosoma cruzi, and three of them (E{3}, E{9} and G{3}) were identified as lead scaffolds for further optimization based on their activity-toxicityprofile. Two promising structures (B{15} and G{15}) showed moderate inhibitory activity againstPlasmodium falciparum. In general, the presence of a benzenesulfonyl moiety improves the antiparasiticactivity of the heterocycles included in this study (with the exception of Trypanosoma brucei rhodesi