Anti-Proliferative and Anti-Migration Activity of Arene-Ruthenium(II) Complexes with Azole Therapeutic Agents

Author(s)

Colina-Vegas, Legna ^[1] ; Oliveira, Katia M. ^[1] ; Cunha, Beatriz N. ^{[1, 2]} ; Cominetti, Marcia Regina ^[3] ; Navarro, Maribel ^{[4, 5]} ; Batista, Alzir Azevedo ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

^[2] IFG, Campus Ceres, BR-7630000 Ceres, Go - Brazil

^[3] Univ Fed Sao Carlos, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

^[4] INMETRO, Inst Nacl Metrol Qualidade & Tecnol, BR-25250020 Xerem, RJ - Brazil

^[5] Univ Fed Juiz de Fora, Dept Quim, ICE, BR-36036900 Juiz De Fora, MG - Brazil

• Document type: Journal article
• Source: INORGANICS; v. 6, n. 4 DEC 2018.
• Web of Science Citations: 2

Abstract

The efficacy of organoruthenium complexes containing ergosterol biosynthesis inhibitors (CTZ: clotrimazole, KTZ: ketoconazole and FCZ: fluconazole) against tumor cells, and their interaction with important macro-biomolecules such as human serum albumin and DNA have been investigated here. Our experimental results indicated that these ruthenium(II) complexes present spontaneous electrostatic interactions with albumin, and act as minor groove binders with the DNA. The ability of these Ru(II)-azole complexes to inhibit the proliferation of selected human tumor and non-tumor cell lines was determined by MTT assay. Complexes {[}RuCl(CTZ)((6)-p-cymene)(PPh3)]PF6 (3) and {[}RuCl(KTZ)((6)-p-cymene)(PPh3)]PF6 (4) were shown to be between 3- and 40-fold more cytotoxic than the free ligands and the positive control cisplatin. Complex 3 was selected to continue studies on the triple negative breast tumor cell line MDA-MB-231, inducing morphological changes, loss of adhesion, inhibition of colony formation, and migration through Boyden chambers, cell cycle arrest in the sub-G1 phase, and a mechanism of cell death by apoptosis. All these interesting results show the potential of this class of organometallic Ru(II) complexes as an antiproliferative agent. (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