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Evaluation of casearin X, piperlonguine and analogues on cancer-associated proteases

Grant number: 16/07816-4
Support type:Scholarships abroad - Research Internship - Scientific Initiation
Effective date (Start): June 01, 2016
Effective date (End): August 31, 2016
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal researcher:Vanderlan da Silva Bolzani
Grantee:Jhennifer Priscila Nastri
Supervisor abroad: Chahrazade El Amri
Home Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Research place: Université Pierre et Marie Curie (Paris 6), France  
Associated to the scholarship:13/01680-5 - Nuclear Magnetic Resonance applied to metabolomic study of Casearia sylvestris, variety C. sylvestris known traditionally as antiulcer, and C. língua variety, BP.IC

Abstract

The extracts of medicinal plants present a great metabolic diversity, and thus have a large amount of bioactive compounds which may have potential as therapeutic agents. They also can be a starting point for the development of new prototypes and play a significant role in drug discovery. The Nucleus for Bioassays, Biosynthesis and Ecophysiology of Natural Products (NuBBE) at the Institute of Chemistry, UNESP (IQ/UNESP) develops phytochemical studies such as isolation and identification of a number of secondary metabolites from biological relevance in plants from the Cerrado biome and Atlantic forest in Brazil. Among the isolated compounds can be highlighted coumarins, peptides, anthraquinones, flavonoids, indole alkaloids, diterpenes, triterpenes and iridoids. Bioassays on these evaluated compounds have demonstrated promising pharmacological properties with a great therapeutic potential. Proteases are one of the molecular targets of current therapeutic interest in order to discover or synthesize potent inhibitors. The interest in these type of enzymes has come up with the results obtained for the therapies of several diseases such as HIV, hypertension, cancer, arthritis and Alzheimer's. Cancer is a leading cause of death worldwide and it should be noted that most of the successful anti-cancer agents came from natural compounds. The aim of this project is to perform protease (proteasome, KLK5, KLK7, MMP9, caspase 2 and caspase 3) activity assays in the compounds casearin X, piperlonguine and 5 new synthetic analogs, in order to find natural potential inhibitors of cancer-associated proteases. To develop the scientific initiation stage abroad a cooperation was stablished with Professor Chahrazade El Amri and Professor M. Reboud-Ravaux at the Molecular and Functional Enzymology Laboratory in The Pierre and Marie Curie University (UPMC), Paris. (AU)

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