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Bioprospection of low molecular weight compounds with antileukemic activity in Bothrops moojeni venom

Grant number: 22/05554-3
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): March 01, 2023
Effective date (End): December 31, 2023
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal Investigator:Suely Vilela
Grantee:Gabriela de Oliveira Almeida
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Leukemia is a very recurrent type of cancer characterized by the involvement of leukocytes. The currently recommended treatment for the disease consists of the use of chemotherapeutic agents that are highly aggressive to the patient, which makes evident the need to develop new, more effective and less toxic therapies. Snake venom is characterized by a complex chemical composition that includes molecules with different physiological and therapeutic actions. This highlights the importance of carrying out studies that identify and characterize new molecules with antitumor activity from this matrix. Thus, the present study aims to isolate molecules of up to 10 kDa from the venom of Bothrops moojeni snakes that have antileukemic action in THP-1 and HL-60 strains. The compounds will be isolated from the crude venom by membrane ultrafiltration and chromatographic methods. Then, the bioprospecting of compounds with antileukemic activity will be carried out, followed by the functional and structural characterization and the mechanism of action of these compounds. Compounds that show cytotoxic activity will be evaluated for induction of apoptosis/necrosis and autophagy. For those that demonstrate anti-migratory activity, inhibition of platelet aggregation, in vitro angiogenesis assay and modulation of cell invasion will be evaluated. Compounds with antiproliferative activity, in turn, will be submitted to cell cycle evaluation. Finally, the bioactive compounds will be submitted to toxicogenomic assays, in addition to being evaluated for toxicity in normal peripheral blood cells and hemolysis capacity, in order to assess their safety. The structures will then be characterized by mass spectrometry, nuclear magnetic resonance and N-terminal sequencing. Therefore, it will be possible to isolate and characterize at least one new molecule with antileukemic therapeutic potential.

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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)
GABRIELA DE OLIVEIRA ALMEIDA; ISADORA SOUSA DE OLIVEIRA; ELIANE CANDIANI ARANTES; SUELY VILELA SAMPAIO. Snake venom disintegrins update: insights about new findings. Journal of Venomous Animals and Toxins including Tropical Diseases, v. 29, . (19/10173-6, 22/05554-3, 20/13176-3, 22/08964-8, 20/15670-5, 21/11936-3, 22/04804-6)

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