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Naturals and semisynthetics metabolites from twigs of Nectandra leucantha Ness & Mart. (Lauraceae): molecular characterization, potential evaluation and mechanism antitumoral against melanoma

Grant number: 15/04143-6
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): June 01, 2015
Effective date (End): March 31, 2018
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal Investigator:João Henrique Ghilardi Lago
Grantee:Fernanda Samara de Sousa
Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil


Malignant melanoma is a highly aggressive and lethal cancer resulted of mutations in the melanocytes, which in the later stages the current therapy is ineffective. Therefore, alternative therapies are required to induce the cytotoxic effects against tumor and at the same time do not damage the patient body. Plants produce and accumulate many compounds which have pharmacological effects, many of which have been exploited in the treatment and prevention of diseases, amongst which cancer. Aiming the chemo-pharmacological study, in this work will be held the isolation and structural characterization of compounds, with in vitro and in vivo antitumoral activity against murine melanoma (B16F10), from branches of Nectandra leucantha Nees & Mart. In view, the hexane and MeOH extracts will be prepared, which will be submitted to evaluation of the cytotoxic potential against murine melanoma cells. The potentially active extract will be subjected to a bioguided fractionation and active metabolites will be purified by chromatographic techniques and their structures determined by spectroscopic and spectrometric techniques. After isolation of bioactive compounds, they will be subject to SAR tests, through different molecular modifications to find out it pharmacophore groups. In continuation, the bioactive compounds will be evaluated for their cytotoxicity mechanism induced in tumor cells, addressing phenotypic, morphological and molecular induced cytotoxicity aspects and its possible anti-tumor effect in vivo. Thus, this project intends to add new prototypes with proven antitumoral activity and chemo-taxonomic contributions for species under study. (AU)

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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)
DE SOUSA, FERNANDA S.; NUNES, EMILENE A.; GOMES, KAIO S.; CERCHIARO, GISELLE; LAGO, JOAO HENRIQUE G.. Genotoxic and cytotoxic effects of neolignans isolated from Nectandra leucantha (Lauraceae). TOXICOLOGY IN VITRO, v. 55, p. 116-123, . (15/11936-2, 14/24475-0, 15/04143-6, 18/07885-1)
DE SOUSA, FERNANDA S.; BALDIM, JOAO L.; AZEVEDO, RICARDO A.; FIGUEIREDO, CARLOS R.; PIEPER, PAULINE; SEAR, CLAIRE E.; ANDERSON, EDWARD A.; LAGO, JOAO HENRIQUE G.. Structure-activity relationship study of cytotoxic neolignan derivatives using multivariate analysis and computation-aided drug design. Bioorganic & Medicinal Chemistry Letters, v. 30, n. 16, . (15/11936-2, 15/04143-6, 16/19269-8, 18/07885-1)
DE SOUSA, FERNANDA S.; GRECCO, SIMONE S.; GIROLA, NATALIA; AZEVEDO, RICARDO A.; FIGUEIREDO, CARLOS R.; LAGO, JOAO HENRIQUE G.. Neolignans isolated from Nectandra leucantha induce apoptosis in melanoma cells by disturbance in mitochondrial integrity and redox homeostasis. Phytochemistry, v. 140, p. 108-117, . (15/04143-6, 15/11936-2)

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