Synthesis and Pharmacological evaluation of new thalidomide/pomalidomide analogues regulators of epigenetic mechanisms

• Grant number: 15/21252-3
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2016
• Effective date (End): February 28, 2018
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Jean Leandro dos Santos
• Grantee: Aline Renata Pavan
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Sickle cell disease (SCD) is a one of the most prevalent genetic and hematologic disease worldwide, which has the hydroxyurea (HU) as the only available drug to the treatment. Despite the beneficial effects of HU in reducing morbidity and mortality associated with the disease, some undesirable features limits its clinical use. Moreover, some individuals do not respond to HU-treatment, justifying the search for new drugs. In this aspect, the reactivation of gamma-globin gene expression, and consequent increase in fetal hemoglobin (HbF) production, by epigenetic mechanisms is a valuable therapeutic intervention. The drugs thalidomide and pomalidomida are known to be able to increase gamma-globin gene expression and fetal hemoglobin levels; however, the exact molecular mechanisms related to these effects are still being investigated. Recent studies show that inhibition of histone deacetylase (HDAC), mainly HDAC-1 and HDAC-2, was shown to be a promising strategy to promote increased gene expression of gamma-globin and HbF production without causing change in the cycle and proliferation cell. In this proposal, using a molecular hybridization approach, we describe the synthesis and pharmacological evaluation of new thalidomide and pomalidomide analogs within HADC inhibitory properties useful as new therapies for SCD treatment.

Scientific publications

(4)

(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)

PAVAN, ALINE RENATA; BERNARDES DA SILVA, GABRIEL DALIO; JORNADA, DANIELA HARTMANN; CHIBA, DIEGO EIDY; DOS SANTOS FERNANDES, GUILHERME FELIPE; CHIN, CHUNG MAN; DOS SANTOS, JEAN LEANDRO. Unraveling the Anticancer Effect of Curcumin and Resveratrol. NUTRIENTS, v. 8, n. 11, NOV 2016. (15/19531-1, 16/08470-4, 14/14980-0, 15/21252-3, 14/24811-0, 14/02240-1)

URIAS, BEATRIZ SILVA; PAVAN, ALINE RENATA; ALBUQUERQUE, GABRIELA RIBEIRO; PROKOPCZYK, IGOR MUCCILO; FERREIRA ALVES, TANIA MARA; FERREIRA DE MELO, THAIS REGINA; RODRIGUES SARTORI, GERALDO; MARTINS DA SILVA, JOAO HERMINIO; CHIN, CHUNG MAN; DOS SANTOS, JEAN LEANDRO. Optimization of Resveratrol Used as a Scaffold to Design Histone Deacetylase (HDAC-1 and HDAC-2) Inhibitors. PHARMACEUTICALS, v. 15, n. 10, p. 18-pg., 2022-10-01. (18/11079-0, 17/07789-0, 18/19523-7, 15/19531-1, 15/21252-3, 19/09456-3)

PAVAN, ALINE RENATA; LOPES, JULIANA ROMANO; DOS SANTOS, JEAN LEANDRO. The state of the art of fetal hemoglobin-inducing agents. EXPERT OPINION ON DRUG DISCOVERY, v. 17, n. 11, p. 15-pg., 2022-11-07. (18/19523-7, 21/10059-9, 20/13279-7, 15/19531-1, 10/12495-6, 12/50359-2, 15/21252-3)

DOS SANTOS FERNANDES, GUILHERME FELIPE; PAVAN, ALINE RENATA; DOS SANTOS, JEAN LEANDRO. Heterocyclic N-oxides - A Promising Class of Agents against Tuberculosis, Malaria and Neglected Tropical Diseases. CURRENT PHARMACEUTICAL DESIGN, v. 24, n. 12, p. 1325-1340, 2018. (15/21252-3, 16/09502-7, 15/19531-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PAVAN, Aline Renata. Design, synthesis and pharmacological evaluation of new phthalimide derivatives as histone deacetylase inhibitors for sickle cell anemia. 2018. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.