SYNTHESIS, CHARACTERIZATION OF ANTI-TUMOR POTENTIAL AND TOXICITY STUDIES OF MELITIN-ANALOGUE PEPTIDES

• Grant number: 23/11588-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2023
• End date: September 30, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry
• Principal Investigator: Norival Alves Santos Filho
• Grantee: Marina Ferreira Marani
• Host Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Cancer, one of the main causes of death in the world, is a genetic disease that is difficult to treat. Because of this, several alternatives for the cure of this disease have already been developed, but most of them have severe side effects, which affect the quality of life of patients affected by the disease; in addition, tumor cells tend to acquire resistance to the administered drugs, thus increasing the search for alternative solutions of antitumor compounds. Among these alternatives, cytotoxic peptides emerged with the premise of being promising chemotherapeutics. These peptides are usually from toxins and animal secretions, or existing in the body's immune system, which bind to receptors or cell membranes and can cause various mechanisms of action to kill cancer cells. However, although promising, studies on antitumor peptides still face major challenges. The most important ones can be mentioned as the high cost of synthesis, the lack of selectivity of cytolytic peptides, which gives these molecules a high toxicity, in addition to the low half-life under physiological conditions, due to the susceptibility to proteases present in organisms. . Within this context, the present proposal aims to synthesize the antimicrobial peptide Melittin, a known cytotoxic peptide, with low selectivity and, consequently, high toxicity; In addition, synthesizing analogue peptides TT1, MCF and MCFA, with the aim of obtaining smaller peptides (which decreases the cost of synthesis), with prominent antitumor activities and lower cytotoxic activities. In addition to analyzing their toxic potential against tumor cells, non-tumor cells and alternative methods.