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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 187, p. 85-96, OCT 2018.
• Web of Science Citations: 3

Abstract

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)

• FAPESP's process: 15/09833-0 - Sustainable delivery system based on biocellulose/metallic complexes containing bioactive ligands
• Grantee: Wilton Rogério Lustri
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/25114-4 - Synthesis of New Ag(I), Cu(II), Pd(II) and Pt(II) complexes based on sulfonamides and derivatives: antibacterial activities and application prospects on skin critically colonized wounds.
• Grantee: Pedro Paulo Corbi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/20882-3 - Metal complexes of sulfamethoxydiazine and sulfadimethoxine: synthesis, characterization and applications as antimicrobial agents for topical use
• Grantee: Douglas Hideki Nakahata
• Support Opportunities: Scholarships in Brazil - Doctorate