Document Detail

Nuclease activity and ultrastructural effects of new sulfonamides with anti-leishmanial and trypanocidal activities.
MedLine Citation:
PMID:  22668836     Owner:  NLM     Status:  Publisher    
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 L. infantum intracellular amastigotes. Compounds 1n and 2d showed nuclease activity in the presence of copper salt analogously 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 provided for sulfonamides 1a, 1n and 2d. Transmission electron microscopic (TEM) analysis of Leishmania infantum promastigotes treated with compounds 1a, 1n and 2d shows an overall cellular disorganization effects which are mainly addressed to DNA bearing structures such as the nucleus, mitochondria and kinetoplast. Disruption of double nuclear membrane and loss of cellular integrity along with accumulation of cytoplasmic electrodense bodies were also frequently observed.
Pablo Bilbao-Ramos; Cristina Galiana-Roselló; M Auxiliadora Dea-Ayuela; Marta González-Alvarez; Celeste Vega; Miriam Rolón; Jorge Pérez-Serrano; Francisco Bolás-Fernández; M Eugenia González-Rosende
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-2
Journal Detail:
Title:  Parasitology international     Volume:  -     ISSN:  1873-0329     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9708549     Medline TA:  Parasitol Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Department of Parasitology, Faculty of Pharmacy, University Complutense of Madrid, Plaza Ramón y Cajal s/n, 28040-Madrid, Spain.
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