Antiparasitic activity and ultrastructural alterations provoked by organoruthenium complexes against Leishmania amazonensis

Autor(es)

Colina-Vegas, Legna ^[1] ; Prado Godinho, Joseane Lima ^{[2, 3, 4]} ; Coutinho, Thallita ^{[2, 3, 4]} ; Correa, Rodrigo S. ^[5] ; de Souza, Wanderley ^{[2, 3, 4]} ; Fernandes Rodrigues, Juliany Cola ^{[2, 3, 4, 6]} ; Batista, Alzir Azevedo ^[1] ; Navarro, Maribel ^{[7, 8]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Carlos, Dept Quim, Sao Carlos, SP - Brazil

^[2] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, Rio de Janeiro - Brazil

^[3] Univ Fed Rio de Janeiro, Inst Nacl Ciencia & Tecnol Biol Estrutural & Bioi, Rio De Janeiro - Brazil

^[4] Univ Fed Rio de Janeiro, Ctr Nacl Biol Estrutural & Bioimagem Cenabio, Rio De Janeiro - Brazil

^[5] Univ Fed Ouro Preto, ICEB, Dept Quim, Ouro Preto, MG - Brazil

^[6] UFRJ Xerem, Nucleo Multidisciplinar Pesquisa, Div Biol, Campus UFRJ Xerem, Duque De Caxias - Brazil

^[7] Univ Fed Juiz de Fora, ICE, Dept Quim, Juiz de Fora, MG - Brazil

^[8] INMETRO, Inst Nacl Metrol Qualidade & Tecnol, Xerem, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NEW JOURNAL OF CHEMISTRY; v. 43, n. 3, p. 1431-1439, JAN 21 2019.
• Citações Web of Science: 1

Resumo

Four new organoruthenium complexes with formula {[}RuCl(eta(6)-p-cymene)(mu-FCZ)](2){[}Cl](2) (1), {[}RuCl(FCZ)(eta(6)-p-cymene)(PPh3)]PF6 (2), {[}RuCl(CTZ)(eta(6)-p-cymene)(PPh3)]PF6 (3) and {[}RuCl(KTZ)(eta(6)-p-cymene)(PPh3)]PF6 (4) (where FCZ: 2-(2,4-difluorophenyl)-1,3-di(1H-1,2,4-triazol-1-yl)-2-propanol, CTZ: 1-{[}(2-chlorophenyl)-diphenylmethyl-1H-imidazole] and KTZ: cis-1-acetyl-4-{[}4-{[}{[}2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmeth yl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) were synthesized, characterized and evaluated as potential inhibitors for Leishmania amazonensis growth by widely reported methods. Complexes 3 and 4 displayed effective IC50 activities against Leishmania amazonensis promastigotes and intracellular amastigotes in the range of nanomolar concentration. Scanning and transmission electron microscopy analysis of Leishmania amazonensis promastigotes after treatment with 300 or 500 nM of complexes 3 and 4 for 48 h showed morphological alterations in the cell surface, a shortening of the flagellum, loss of mitochondrial matrix, disorganization of the kDNA and abnormal chromatin condensation. Thus, our strategy of incorporating a ruthenium atom into the structure of clinical drugs to improve their efficacy continues to demonstrate suitability for metallodrug discovery purposes. (AU)

• Processo FAPESP: 17/23254-9 - Determinação quantitativa e imagem celular de Cu, Ru e Pt em células individuais usando Ablação a laser acoplado ao ICP-MS
• Beneficiário: Legna Andreina Colina Vegas
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 16/23130-5 - Determinação da biodistribuição celular de Cu, Ru e Pt em células humanas tumorais e não tumorais de mama mediante a técnica de espectrometria de massas com plasma acoplado indutivamente
• Beneficiário: Legna Andreina Colina Vegas
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado