Sulfonamide-containing copper(ii) complexes: new insights on biophysical interactions and antibacterial activities

Autor(es)

Nakahata, Douglas H. ; de Paiva, Raphael E. F. ; Lustri, Wilton R. ; Corbi, Pedro P.

• Tipo de documento: Artigo Científico
• Fonte: NEW JOURNAL OF CHEMISTRY; v. 44, n. 40, p. 9-pg., 2020-10-28.

Resumo

Copper(ii)-sulfonamide-((NN)-N-boolean AND) complexes are a promissing class of compounds resulting from the combination of bioactive organic drugs with the Cu-((NN)-N-boolean AND) motif. Here, we expand on the studies of three of such compounds that we had previously reported to be effective metallonucleases with promising antiproliferative activities. Since the compounds were previously shown to interact with DNA mostly in a non-covalent form, in this study we investigated their interactions with specific nucleotides to evaluate possible ligand replacement and preferential purine or pyrimidine base binding. Results showed partial ligand dissociation followed by non-preferential nucleotide binding in the conditions of mass spectrometric experiments. Additional biophysical studies of the interaction between the complexes and serum albumin, which is an important class of carriers of metallodrugs in plasma were performed and described for the first time here. Fluorescence spectroscopy indicated binding of the compounds to albumin, while dynamic light scattering (DLS) and circular dichroism (CD) data indicated no significant alteration of protein secondary structure or agglomeration. The compounds showed no protease activity on serum albumin or on lysozyme, a smaller protein, even in the presence of a reducing agent. The absence of protease activity is an important factor when it is considered the compounds can be transported by serum albumin and, when combined with data we reported previously, also indicates that DNA is more prone to cleavage by the compounds. Since both sulfonamides and copper(ii) complexes have antibacterial effects, here we investigated the antibacterial activity of the complexes on three prevalent bacterial strains (Staphylococcus aureus,Escherichia coliandPsedomonas aeruginosa) with results indicating that the compounds are more active towards the Gram-positiveS. aureusstrain. The combination of the Cu-((NN)-N-boolean AND) motif with synergic sulfonamide ligands leads to metallonucleases with potential application in various biological endpoints. (AU)

• Processo FAPESP: 15/09833-0 - Dispositivos de liberação sustentada baseados em biocelulose/complexos metálicos com ligantes bioativos
• Beneficiário: Wilton Rogério Lustri
• Modalidade de apoio: Auxílio à Pesquisa - Regular
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• Beneficiário: Douglas Hideki Nakahata
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 18/12062-4 - Síntese, caracterização e estudos de interação com biomoléculas de complexos metálicos contendo ligantes biologicamente ativos: uma estratégia na preparação de novos agentes com atividades antibacterianas e antivirais
• Beneficiário: Pedro Paulo Corbi
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/21537-6 - Aplicações de ligantes imínicos polidentados na modulação da reatividade de íons cobre em doenças relacionadas a inflamação e em reações de acoplamento bio-ortogonais
• Beneficiário: Raphael Enoque Ferraz de Paiva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/12590-0 - Síntese de complexos metálicos com ligantes bioativos N,N ou N,O-coordenantes para utilização em dispositivos de liberação sustentada baseados em celulose bacteriana
• Beneficiário: Wilton Rogério Lustri
• Modalidade de apoio: Auxílio à Pesquisa - Regular
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• Beneficiário: Pedro Paulo Corbi
• Modalidade de apoio: Auxílio à Pesquisa - Regular