Sulfonamide-containing copper(II) metallonucleases: Correlations with in vitro antimycobacterial and antiproliferative activities

Autor(es)

Nakahata, Douglas H. ^[1] ; de Paiva, Raphael E. F. ^[1] ; Lustri, Wilton R. ^[2] ; Ribeiro, Camila M. ^[3] ; Pavan, Fernando R. ^[3] ; da Silva, Gisele G. ^{[4, 5, 6]} ; Ruiz, Ana L. T. G. ^{[5, 6]} ; de Carvalho, Joao E. ^[5] ; Corbi, Pedro P. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Inst Chem, BR-13083970 Campinas, SP - Brazil

^[2] Univ Araraquara, Biol & Hlth Sci Dept, UNIARA, BR-14801320 Araraquara, SP - Brazil

^[3] Sao Paulo State Univ, UNESP, Sch Pharmaceut Sci, BR-14800901 Araraquara, SP - Brazil

^[4] Univ Estadual Campinas, UNICAMP, Piracicaba Dent Sch, Dept Physiol Sci, BR-13414903 Piracicaba, SP - Brazil

^[5] Univ Estadual Campinas, UNICAMP, Fac Pharmaceut Sci, BR-13081970 Campinas, SP - Brazil

^[6] Univ Estadual Campinas, UNICAMP, Chem Biol & Agr Pluridisciplinary Res Ctr CPQBA, BR-13148218 Paulina, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Inorganic Biochemistry; v. 187, p. 85-96, OCT 2018.
• Citações Web of Science: 2

Resumo

The bis-(1,10-phenanthroline)copper(I) complex, {[}Cu(I)(phen)(2)](+), was the first copper-based artificial nuclease reported in the literature. The biological and ligand-like properties of sulfonamides make them good candidates for fine-tuning the reactivity of the {[}Cu(phen)(2)] motif with biomolecules. In this context, we developed three novel copper(II) complexes containing the sulfonamides sulfameter (smtrH) and sulfadimethoxine (sdmxH) and (KN)-bidentate ligands (2,2'-biyridine or 1,10-phenantroline). The compounds were characterized by chemical and spectroscopic techniques and single-crystal X-ray crystallography. When targeting plasmid DNA, the phencontaining compounds {[}cu(smtr(-))(2)(phen)1 (1) and {[}Cu(sdmx(-))(2)(phen)1 (2) demonstrated nuclease activity even in the absence of reducing agents. Addition of ascorbic acid resulted in a complete cleavage of DNA by 1 and 2 at concentrations higher than 10 M. Experiments designed to evaluate the copper intermediates involved in the nuclease effect after reaction with ascorbic acid identified at least the {[}Cu(I)(N<\^{}>N)(2)](+), {[}Cu(I)(sulfa) (N<\^{}>N)](+) and {[}Cu(I)(sulfa)2](+) species. The compounds interact with DNA via groove binding and intercalation as verified by fluorescence spectroscopy, circular dichroism (CD) and molecular docking. The magnitude and preferred mode of binding are dependent on the nature of both N<\^{}>N ligand and the sulfonamide. The potent nuclease activity of compounds 1 and 2 are well correlated with their antiproliferative and anti-M. tuberculosis profiles. The results presented here demonstrated the potential for further development of copper(II)-sulfonamide-(N<\^{}>N) complexes as multipurpose metallodrugs. (AU)

• Processo FAPESP: 15/20882-3 - Complexos metálicos com sulfametoxidiazina e sulfadimetoxina: síntese, caracterização e aplicações como agentes antimicrobianos para uso tópico
• Beneficiário: Douglas Hideki Nakahata
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/09833-0 - Dispositivos de liberação sustentada baseados em biocelulose/complexos metálicos com ligantes bioativos
• Beneficiário: Wilton Rogério Lustri
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/25114-4 - Preparação de novos complexos de Ag(I), Cu(II), Pd(II) e Pt(II) à base de sulfonamidas e derivados: estudos de atividade antibacteriana e perspectivas de aplicação em lesões de pele criticamente colonizadas
• Beneficiário: Pedro Paulo Corbi
• Linha de fomento: Auxílio à Pesquisa - Regular