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Synthesis and biological evaluation of hybrid inhibitors for the treatment of hematologic malignancies

Grant number: 22/12468-6
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2022
Effective date (End): November 30, 2023
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Roberto Parise Filho
Grantee:Vinícius Albuquerque Moreira de Souza
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil


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 synthesis of hybrid dual-action PI3K´-HDAC6 inhibitors, as well as the biological evaluation against a panel of hematological and solid tumors.

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