Investigation of the interaction of dipyrone and diclofenac on the PAF AH enzyme in silico and in vitro and the evaluation of the adjuvant potential for the treatment of tumors.

• Grant number: 24/17961-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marcos Hikari Toyama
• Grantee: Danillo Ravazani Silva Lima
• Host Institution: Instituto de Biociências (IB-CLP). Universidade Estadual Paulista (UNESP). Campus Experimental do Litoral Paulista. São Vicente , SP, Brazil

Abstract

This study focuses on evaluating the interaction between non-steroidal anti-inflammatory drugs (NSAIDs), such as diclofenac and dipyrone, and the enzyme phospholipase A2 associated with lipoproteins (PAF-AH), also known as PAF-AH, which plays a role fundamental in modulating the inflammatory response and maintaining homeostasislipid. PAF-AH, involved in the hydrolysis of platelet activating factor (PAF) and othersphospholipids, is especially relevant in the context of tumor environmentspro-inflammatory, where changes in cell signaling pathways can influenceits expression and activity.Our objective is to investigate how NSAIDs can affect the enzymatic activity ofPAF-AH and, consequently, interfere with tumor development, addressing aspectssuch as cell proliferation, angiogenesis, tumor invasion and resistance to therapies. The research begins with in silico analyzes to elucidate molecular interactionspotential and the inhibition capacity of these NSAIDs on the enzyme. Then rehearsalsIn vitro enzymatic tests will confirm the computationally observed inhibitory activities.Once the effectiveness of NSAIDs in inhibiting PAF-AH has been established, we will move on to trials in tumor cell cultures, aiming to evaluate the impact of these compounds on viability of cancer cells and explore possible synergies with treatmentsexisting antitumor drugs.Through this integrated approach, we seek not only to better understandthe role of PAF-AH in cancer, but also investigate the possibility of using NSAIDsas supporting agents, aiming to enhance the effects of antitumor treatmentsand open new fronts in therapeutic strategies against cancer.