Studies on the structure and activity of RuI/arene/mercaptoligand complexes against cancer

• Grant number: 23/10889-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2023
• End date: November 30, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Agreement: CNPq - Pronex
• Principal Investigator: Javier Alcides Ellena
• Grantee: Camila Batista Pinto
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant: 17/15850-0 - X-ray diffraction as a tool in potential drug development, AP.TEM

Abstract

This work plan deals with obtaining and characterizing ruthenium II semi-sandwich complexes containing ligands of biological interest, as new candidates for metallopharmaceuticals, being an integral part of the thematic project "X-Ray Diffraction as a Tool in the Development of Potential Drugs" (2017/15850-0). In the synthesis stage, it is intended to carry out a "screening" to evaluate the viability of coordination of mercaptoligands, which are derivatives of mercaptopyridines and mercaptopyrimidines, with ruthenium II precursors of general formula [Ru(h6-p-cymene)Cl2] 2 and [Ru(h6-p-cymene)Cl2(P)] where P refers to monophosphines. The synthesized compounds will be characterized by techniques such as 1H, 13C and 31P{1H} nuclear magnetic resonance spectroscopy, cyclic and differential pulse voltammetry, conductimetry, absorption spectroscopy in the ultraviolet/visible/infrared region and elemental analysis. In addition, it will dedicate itself to the characterization of compounds in the solid state, mainly by X-ray diffraction by single crystals (equipment operation, collection and refinement of data), the structural and crystallographic properties exhibited by these complexes and others belonging to the thematic project. , and from the structural information to elucidate some physicochemical properties of them. Subsequently, we intend to study the possible interactions of these complexes with biomolecules such as: DNA and HSA. The influence of the compounds on the cell cycle, annexin V apoptosis assay, quantification of reactive oxygen species, as well as determination of proteins related to apoptosis will also be evaluated. The results obtained will be compared with each other and with data from the literature, seeking a better understanding of the molecular regions responsible for their biological, chemical and structural properties, in order to explore how the compounds can interact with them and elucidate their mechanisms of action. (AU)