Nuclease activity and ultrastructural effects of new sulfonamides with anti-leishmanial and trypanocidal activities

Parasitology International
Pablo Bilbao-RamosM Eugenia González-Rosende

Abstract

Our aim was to evaluate the in vitro efficacy of a series of N-benzenesulfonamides of amine substituted aromatic rings, sulfonamides 1-6, against Trypanosoma cruzi and Leishmania spp. and to compare their trypanocidal and leishmanicidal profile. In order to elucidate the probable mechanism of action, the interaction of selected sulfonamides with pUC18 plasmid DNA was investigated by nuclease activity assays. In addition, the cellular targets of these sulfonamides in treated parasites were also searched by transmission and scanning electron microscopy. The most active compounds 4-nitro-N-pyrimidin-2-ylbenzenesulfonamide 1a and 4-chloro-N-5-methyl-thiazol-2-yl-benzenesulfonamide 2d displayed significant in vitro activity against Leishmania spp. promastigotes, without toxicity to J774 macrophages. Selected sulfonamides 1a, 4-nitro-N-pyrazin-2-yl-benzenesulfonamide 1n and 2d were also active against Leishmania infantum intracellular amastigotes. Compounds 1n and 2d showed nuclease activity in the presence of copper salt analogous to our previous results with sulfonamide 1a. Mechanistic data reveal the involvement of a redox process. Evidence for the formation of reactive oxygen species (ROS) responsible for DNA strand scission is p...Continue Reading

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Citations

Jun 19, 2016·European Journal of Medicinal Chemistry·M Auxiliadora Dea-AyuelaMiguel A González-Cardenete
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May 12, 2018·Molecular Diversity·Juan Carlos Sánchez-SalgadoYareli Rojas-Aguirre
Sep 15, 2018·The Journal of Venomous Animals and Toxins Including Tropical Diseases·Carina Agostinho RodriguesDaniela Gonçales Galasse Rando
Mar 25, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pablo Bilbao-RamosM Auxiliadora Dea-Ayuela
Mar 7, 2021·Antibiotics·Miguel A González-CardeneteM Auxiliadora Dea-Ayuela

Related Concepts

Ro 7-1051
Miltex
Schizonticides
Cell Survival
Alkaline DNase
Macrophage
Scanning Electron Microscopy
Nitroimidazoles
Phosphorylcholine
Sulfonamides

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