Synthesis and biological evaluation of purine-benzohydroxamates as potential inhibitors of PI3K and HDAC6 for the treatment of hematologic malignancies

• Grant number: 23/13499-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2023
• End date: November 30, 2024
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Roberto Parise Filho
• Grantee: João Pedro Freitas Verotti
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Several studies pointed out the advantages of the multi-target approach in cancer treatment. In this context, the hybridization of pharmacophoric groups with distinct action can be a valuable strategy in the discovery of molecules capable of inhibiting two - or more - cellular signaling pathways, increasing the efficacy, and improving the therapeutic regimen of chemotherapy treatment. Phosphoinositide 3-kinase (PI3K) and histone deacetylase 6 (HDAC6) inhibitors, when used in combination, have shown synergism of action and increased antineoplastic efficacy, especially in hematological tumors. Herein, this project aims the design and synthesis of hybrid dual-action PI3K´-HDAC6 inhibitors, as well as the biological evaluation against a panel of hematological and solid tumors.