Increased ROS generation causes apoptosis-like death: Mechanistic insights into the anti-Leishmania activity of a potent ruthenium(II) complex

Author(s):Show less -

Costa, Monica Soares ^[1] ; Goncalves, Yasmim Garcia ^[2] ; Teixeira, Samuel Cota ^[3] ; de Oliveira Nunes, Debora Cristina ^[1] ; Lopes, Daiana Silva ^{[1, 4]} ; da Silva, Claudio Vieira ^[3] ; da Silva, Marcelo Santos ^[5] ; Borges, Bruna Cristina ^[6] ; Barbosa Silva, Marcelo Jose ^[6] ; Rodrigues, Renata Santos ^[1] ; Rodrigues, Veridiana de Melo ^[1] ; Von Poelhsitz, Gustavo ^[2] ; Geraldo Yoneyama, Kelly Aparecida ^[1]

Affiliation

^[1] Univ Fed Uberlandia, Inst Biotecnol, Lab Bioquim & Toxinas Anim, Uberlandia, MG - Brazil

^[2] Univ Fed Uberlandia, Inst Quim, Uberlandia, MG - Brazil

^[3] Univ Fed Uberlandia, Inst Ciancias Biomed, Lab Tripanosomatideos, Uberlandia, MG - Brazil

^[4] Univ Fed Bahia, Inst Multidisciplinar Saude, Campus Anisio Teixeira, Vitoria Da Conquista - Brazil

^[5] Univ Sao Paulo, Inst Butantan, LECC, Ctr Toxinas Resposta Imune & Sinalizacao Celular, Sao Paulo - Brazil

^[6] Univ Fed Uberlandia, Inst Ciencias Biomed, Lab Osteoimunol & Imunol Tumores, Uberlandia, MG - Brazil

• Document type: Journal article
• Source: Journal of Inorganic Biochemistry; v. 195, p. 1-12, JUN 2019.
• Web of Science Citations: 0

Abstract

Some metallodrugs that exhibit interesting biological activity contain transition metals such as ruthenium, and have been extensively exploited because of their antiparasitic potential. In previous study, we reported the remarkable anti-Leishmania activity of precursor cis-{[}(RuCl2)-Cl-II(dppm)(2)], where dppm = bis(diphenylphosphino) methane, and new ruthenium(II) complexes, cis-{[}Ru-II(eta(2)-O2CC10H13)(dppm)(2)]PF6 (bbato), cis-{[}Ru-II(eta(2)-O2CC7H7S)(dppm)(2)]PF6 (mtbato) and cis-{[}Ru-II(eta(2)-O2CC7H7O2)(dppm)(2)]PF6 (hmxbato) against some Leishmania species. In view of the promising activity of the hmxbato complex against Leishmania (Leishmania) amazonensis promastigotes, the present work investigated the possible parasite death mechanism involved in the action of this hmxbato and its precursor. We report, for the first time, that hmxbato and precursor promoted an increase in reactive oxygen species production, depolarization of the mitochondria] membrane, DNA fragmentation, formation of a pre-apoptotic peak, alterations in parasite morphology and formation of autophagic vacuoles. Taken together, our results suggest that these ruthenium complexes cause parasite death by apoptosis. Thus, this work provides relevant knowledge on the activity of ruthenium(II) complexes against L. (L.) amazonensis. Such information will be essential for the exploitation of these complexes as future candidates for cutaneous leishmaniasis treatment. (AU)

• FAPESP's process: 14/24170-5 - DNA replication dynamics in Trypanosoma cruzi: licensing and replication rate characterization
• Grantee: Marcelo Santos da Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral