Synthesis of acid ceramidase inhibitors as possible tools for the oral treatment of prostate cancer

• Grant number: 22/01239-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2022
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Daniel Fábio Kawano
• Grantee: Xisto Antonio de Oliveira Neto
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 24/21384-6 - Inhibition of enzymes related to the lipid metabolism for the treatment of acute myeloid leukemia, BE.EP.DR

Abstract

Prostate cancer is the second most common cancer among men, with the development of metastases being the main cause of death associated with it. In this sense, the involvement of adjacent lymph nodes, liver, lungs and, especially, bones is common, with 9 out of 10 patients with metastatic prostate cancer manifesting bone tissue involvement. Although androgenic castration therapy is effective and safe in the early stages of the disease, it can induce the repopulation of the tumor mass with resistant cells, as well as their metastatic derivatives. In these cases, chemotherapy with docetaxel or mitoxantrone can be used, but the average survival of these patients does not reach 18 months. Interestingly, the inhibition of acid ceramidases allows sensitization of prostate cancer cells to chemo and radiotherapy, thereby reducing tumor growth and preventing cancer recurrence. In this context, this research proposes the development of covalent inhibitors of these enzymes that have the necessary metabolic stability to be used orally in the treatment of prostate cancer, ideal characteristics that none of the compounds described in the literature currently have.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SCHNEIDER ALVES, ANNA CAROLINA; CARDOSO, RAQUEL SOARES; DE OLIVEIRA NETO, XISTO ANTONIO; KAWANO, DANIEL FABIO. Uncovering the Potential of Lipid Drugs: A Focus on Transient Membrane Microdomain-targeted Lipid Therapeutics. MINI-REVIEWS IN MEDICINAL CHEMISTRY, v. 22, n. 18, p. 14-pg., 2022-01-01. (18/08585-1, 18/22817-2, 22/01239-6, 17/05876-2)