"Ru(II) complexes containing phytocompounds or mercaptes as ligands: A rational strategy for obtaining potential metallopharmaceuticals"

• Grant number: 25/01813-2
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: April 01, 2025
• End date: May 31, 2028
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
• Principal Investigator: Alzir Azevedo Batista
• Grantee: Rafael Wendel Rodrigues Santana
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 23/02475-8 - Phosphine Ru(II) complexes with naphthoquinones and derivatives: potential anticancer, estudies in vitro and in vivo, AP.R

Abstract

Cancer is one of the main causes of death in the world, which is why many researchers are looking for new chemotherapy drugs and therapeutic processes. In this sense, medicinal inorganic chemistry presents itself as a good field of study. In particular, ruthenium complexes have been widely explored for the development of candidates for new anticancer metallopharmaceuticals, because of promising properties attributed to ruthenium, such as its ability and ease to reach various oxidation states in biological fluids and its ability to interact with biomolecules. The use of phosphinic ligands and bioactive molecules has proven to be a good strategy for obtaining complexes with improved antitumor activities. Therefore, the present work is dedicated to obtaining and characterizing new ruthenium complexes containing 2,2'-bipyridylamine (bpa) and 1,4-bis(diphenylphosphine)butane (dppb), divided into 3 distinct series of complexes. Series 1: complexes with the general formula [Ru(O-O)(dpa)(dppb)]PF6, where (O-O) = natural products, such as lausone, lapachol, quercetin, hespertin and rutin; series 2: complexes with the general formula [Ru(N-S)(dpa)(dppb)]PF6, where N-S = mercaptopyridines such as 2-mercaptopyridine, 2-mercaptopyrimidine, 2-mercaptothiazoline, 4,6 diamino-2-mercaptopyrimidine and 6-mercaptopyridine-3-carboxylic acid; series 3: complexes of the type [Ru(bpa)2(N-S)]PF6 and [Ru(bpa)2(O-O)]PF6. After characterization, the complexes will be evaluated for their cytotoxic activities against tumor and non-tumor cell lines. Interaction studies will be carried out with DNA, the main target of anticancer drugs such as cisplatin, and with Human Serum Albumin (HSA), a nutrient transport protein and molecules of biological interest, with the aim of analyzing the biological properties of the compounds with a view to searching for possible mechanisms of action.