The nicotinamide ruthenium(II) complex induces the production of reactive oxygen species (ROS), cell cycle arrest, and apoptosis in melanoma cells

Author(s)

Silva, Henrique Vieira Reis ; da Silva, Guilherme Alvaro Ferreira ; Zavan, Bruno ; Machado, Rafael Pereira ; de Araujo-Neto, Joao Honorato ; Ellena, Javier Alcides ; Ionta, Marisa ; Fraza, Marilia Imaculada ; Doriguetto, Antonio Carlos

• Document type: Journal article
• Source: Polyhedron; v. 231, p. 17-pg., 2023-01-03.

Abstract

A set of new ruthenium complexes, [RuCl(NIC)(dppb)(4,4 '-Me-bipy)]PF6 (C1), [RuCl(NIC)(dppb)(4,4 '-Methoxybipy)]PF6 (C2), and [RuCl(NIC)(dppb)(5,5 '-Me-bipy)]PF6 (C3), where NIC = 3-pyridinecarboxamide, 4,4 '-Mebipy = 4,4 '-dimethyl-2,2 '-bipyridine, 4,4 '-Methoxy-bipy = 4,4 '-dimethoxy-2,2 '-bipyridine, and 5,5 '-Me-bipy = 5,5 '-dimethyl-2,2 '-bipyridine were synthesized and characterized by elemental analysis, UV/Vis and infrared spectroscopy, 31P{1H},1H, 13C{1H} nuclear magnetic resonance (NMR), and cyclic voltammetry. In addition, the structure of [RuCl(NIC)(dppb)(4,4 '-Me-bipy)]PF6 was confirmed by single crystal X-ray diffraction (XRD). The solution stability study of C1-C3 showed the formation of pyridine which was coordinated due to solvent protic attacked to nicotinamide, and an elimination reaction of a carbamate group was observed. C1-C3 interacted with DNA through intercalation, electrostatic forces of attraction, or hydrogen bonding. The complexes interacted, moderately and spontaneously, with HSA, mainly through Van der Waals and hydrogen bond interactions. An in vitro evaluation of the (C1-C3) complexes revealed a cytotoxicity against MCF-7, HepG2, A549, SK-MEL-147, WM1366, and CHL-1. A higher cytotoxicity was observed for compound (C3) against melanoma cell cancer (CHL-1). Moreover, the (C3) complex inhibited the clonogenic capacity and cell cycle progression of CHL-1 cells and induced apoptosis involving the production of reactive oxygen species (ROS). [RuCl(py)(dppb)(5,5 '-Mebipy)]PF6 presented a very close C3 cytotoxicity against melanoma cell cancer (CHL-1). (AU)

• FAPESP's process: 17/15850-0 - X-ray diffraction as a tool in potential drug development
• Grantee: Eduardo Ernesto Castellano
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 21/04876-4 - Studies on structure & activity of RuII / arene / mercaptoligants complexes against cancer
• Grantee: João Honorato de Araujo Neto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral