title: Sulfonamide-metal complexes endowed with potent anti-Trypanosoma cruzi activity.
abstract: In this article, we describe that mononuclear complexes composed of (5-chloro-2-hydroxybenzylidene)aminobenzenesulfonamides (L1-3) of general formula (L2(M)2H2O, where M is Co, Cu, Zn, Ni or Mn) reduced epimastigote proliferation and were found cidal for trypomastigotes of Trypanosoma cruzi Y strain. Complexes C5 and C11 have IC50 of 2.7 ± 0.27 and 4.8 ± 0.47 µM, respectively, for trypomastigotes, when the positive control Nifurtimox, which is also an approved drug for Chagas disease, showed IC50 of 2.7 ± 0.25 µM. We tested whether these complexes inhibit the enzyme T. cruzi trypanothione reductase or acting as DNA binders. While none of these complexes inhibited trypanothione reductase, we observed some degree of DNA binding, albeit less pronounced than observed for cisplatin in this assay. Unfortunately, most of these complexes were also toxic for mouse splenocytes. Along with the present studies, we discuss a number of interesting structure-activity relationships and chemical features for these metal complexes, including computational calculations.
authors: Department of Chemistry, Bahauddin Zakariya University , Multan , Pakistan .
authors: Zahid H
authors: ZH
authors: Chohan
authors: Marcelo Zaldini
authors: MZ
authors: Hernandes
authors: Fabricio R
authors: FR
authors: Sensato
authors: Diogo Rodrigo Magalhaes
authors: DR
authors: Moreira
authors: Valéria Rego Alves
authors: VR
authors: Pereira
authors: Juliana Kelle de Andrade Lemoine
authors: JK
authors: Neves
authors: Andresa Pereira
authors: AP
authors: de Oliveira
authors: Beatriz Coutinho
authors: BC
authors: de Oliveira
authors: Ana Cristina Lima
authors: AC
authors: Leite
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000981:Antiprotozoal Agents; D056831:Coordination Complexes; D013449:Sulfonamides; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase