In vivo EVALUATION OF THE ANTIMELANOMA EFFECT OF RUTHENIUM COMPLEX [Ru(2mq)(dppen)2]PF6

• Grant number: 24/14628-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: July 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Heloiza Diniz Nicolella
• Grantee: Fernanda de Freitas Noronha
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 17/15850-0 - X-ray diffraction as a tool in potential drug development, AP.TEM

Abstract

Melanoma is a type of skin cancer caused by the uncontrolled proliferation of melanocytes, affecting mainly young and middle-aged individuals. In Brazil, 8.6 thousand cases are registered annually, while worldwide the number reaches 325 thousand. This cancer, which can be triggered by genetic factors, as well as environmental reasons and lifestyle of the individual, is responsible for about 70% of deaths related to skin cancer, being characterized by its complexity and genetic heterogeneity, which leads to resistance to therapy. Given this scenario, there is a pressing need to develop new therapies for the treatment of melanoma that are more effective and with less systemic toxicity. Thus, ruthenium complexes are promising candidates for chemotherapy, due to their multifunctional biochemical properties. In addition, previous studies conducted by our research group revealed an antimelanoma effect of ruthenium complex [Ru(2mq)(dppen)2]PF6 in vitro. In this sense, the present work aims to evaluate the antimelanoma potential of [Ru(2mq)(dppen)2]PF6 in an in vivo test system. For this, the singenic model of murine melanoma will be used, so that melanoma cells (B16-F10) will be implanted in C57BL/6 mice, which will be submitted to treatment with the complex [Ru(2mq)(dppen)2]PF6, for five consecutive days, intratumoral. Additionally, toxicological monitoring will be performed, through the evaluation of the biochemical parameters of hepate and nephrotoxicity, as well as genotoxic damage by the micronucleus assay and body and tissue mass of C57BL/6 mice with induced melanoma. Finally, the mechanism of action involved in the possible antimelanoma effect of the complex [Ru(2mq)(dppen)2]PF6, by immunohistochemistry, will be evaluated by determining the level of expression of Nrf2. Thus, the experimental model will allow to confirm the effects observed in vitro, through a test system that has pharmacokinetic and pharmacodynamic influence, contributing to the advancement of research in search of new therapies for the treatment of melanoma.