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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: NEW JOURNAL OF CHEMISTRY; v. 43, n. 3, p. 1431-1439, JAN 21 2019.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 17/23254-9 - Quantitative determination and cellular imaging of Cu, Ru and Pt in single cells using Laser Ablation-ICP-Mass Spectrometry
• Grantee: Legna Andreina Colina Vegas
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 16/23130-5 - Determination of cellular biodistribution of Cu, Ru and Pt in human tumor and non tumor breast cells by Inductively Coupled Plasma Mass Spectrometry
• Grantee: Legna Andreina Colina Vegas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral