Identification and preliminary structure-activity relationship studies of novel pyridyl sulfonamides as potential Chagas disease therapeutic agents |
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| Authors: | Raiza Brandão Peres Asma Inam Ullah Ludmila Ferreira de Almeida Fiuza Patricia Bernardino Silva Marcos M Batista Olivia Corcoran Tummala Rama Krishna Reddy Maria de Nazaré Correia Soeiro |
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| Institution: | 1. Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;2. The Medicines Research Group, School of Health, Sport and Bioscience, College of Applied Health and Communities, University of East London, Stratford Campus, Water Lane, E15 4LZ, UK |
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| Abstract: | Chagas disease is a neglected pathology responsible for about 12,000 deaths every year across Latin America. Although six million people are infected by the Trypanosoma cruzi, current therapeutic options are limited, highlighting the need for new drugs. Here we report the preliminary structure activity relationships of a small library of 17 novel pyridyl sulfonamide derivatives. Analogues 4 and 15 displayed significant potency against intracellular amastigotes with EC50 of 5.4?µM and 8.6?µM. In cytotoxicity assays using mice fibroblast L929 cell lines, both compounds indicated low toxicity with decent selectivity indices (SI) >36 and?>23 respectively. Hence these compounds represent good starting points for further lead optimization. |
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| Keywords: | Chagas disease Pyridyl sulfonamides SAR studies Drug likeness Pharmacokinetic properties |
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