Identification and preliminary structure-activity relationship studies of novel pyridyl sulfonamides as potential Chagas disease therapeutic agents

Bioorg Med Chem Lett. 2018 Jun 15;28(11):2018-2022. doi: 10.1016/j.bmcl.2018.04.064.

Raiza Brandão Peres ¹, Asma Inam Ullah ², Ludmila Ferreira de Almeida Fiuza ¹, Patricia Bernardino Silva ¹, Marcos M Batista ¹, Olivia Corcoran ², Tummala Rama Krishna Reddy ³, Maria de Nazaré Correia Soeiro ¹

Affiliations

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.
3 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. Electronic address: [email protected].

PMID: 29748049 DOI: 10.1016/j.bmcl.2018.04.064

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.

Keywords

Chagas disease; Drug likeness; Pharmacokinetic properties; Pyridyl sulfonamides; SAR studies; Trypanosoma cruzi.

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