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

Article


Peres, Raiza Brandão, Ullah, Asma Inam, de Almeida Fiuza, Ludmila Ferreira, Silva, Patricia Bernardino, Batista, Marcos M., Corcoran, O., Reddy, T. and de Nazaré Correia Soeiro, Maria 2018. Identification and preliminary structure-activity relationship studies of novel pyridyl sulfonamides as potential Chagas disease therapeutic agents. Bioorganic & Medicinal Chemistry Letters. 28 (11), pp. 2018-2022.
AuthorsPeres, Raiza Brandão, Ullah, Asma Inam, de Almeida Fiuza, Ludmila Ferreira, Silva, Patricia Bernardino, Batista, Marcos M., Corcoran, O., Reddy, T. and de Nazaré Correia Soeiro, Maria
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.

JournalBioorganic & Medicinal Chemistry Letters
Journal citation28 (11), pp. 2018-2022
ISSN0960-894X
Year2018
PublisherElsevier
Accepted author manuscript
License
Accepted author manuscript
License
Digital Object Identifier (DOI)doi:10.1016/j.bmcl.2018.04.064
Web address (URL)https://doi.org/10.1016/j.bmcl.2018.04.064
Publication dates
Online30 Apr 2018
Print15 Jun 2018
Publication process dates
Deposited29 May 2018
Accepted27 Apr 2018
Accepted27 Apr 2018
FunderFundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação Oswaldo Cruz
PTDIS
PAEF/CNPq/Fiocruz CAPES
University of East London
Copyright information© 2018 Elsevier
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