Terpenoids from Leaves of Guarea macrophylla Display In Vitro Cytotoxic Activity and Induce Apoptosis In Melanoma Cells

Autor(es)

Conserva, Geanne Alexandra A. ^{[1, 2]} ; Girola, Natalia ^[3] ; Figueiredo, Carlos R. ^{[3, 4]} ; Azevedo, Ricardo A. ^[5] ; Mousdell, Sasha ^[4] ; Sartorelli, Patricia ^[1] ; Soares, Marisi G. ^[6] ; Antar, Guilherme M. ^[7] ; Lago, Joao Henrique G. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Sao Paulo, SP - Brazil

^[2] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Ave Estados 5001, BR-09210580 Santo Andre, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo, SP - Brazil

^[4] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, Merseyside - England

^[5] Univ Sao Paulo, Inst Ciencias Biomed, Lab Imunol Tumores, Sao Paulo - Brazil

^[6] Univ Fed Alfenas, Inst Quim, Alfenas, MG - Brazil

^[7] Univ Sao Paulo, Inst Biociencias, Dept Bot, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Planta Medica; v. 83, n. 16, p. 1289-1296, NOV 2017.
• Citações Web of Science: 2

Resumo

Guarea macrophylla is a Brazilian plant species that has been used in folk medicine to treat a range of diseases. Our ongoing work focuses on the discovery of new bioactive natural products derived from Brazilian flora. The current study describes the identification of cytotoxic compounds from the EtOH extract of leaves from G. macrophylla using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of four compounds: cycloart-23E-ene-3 beta,25-diol (1), (23S{*},24S{*})-dihydroxycicloart-25-en-3-one (2), isopimara-7,15-diene-2 alpha,3 beta-diol (3), and isopimara-7,15-dien-3 beta-ol (4), in which 2 and 3 are identified as new derivatives. In vitro assays were conducted to evaluate the cytotoxic activity of compounds 1-4 against a panel of cancer cell lines and to determine the possible mechanism(s) related to the activity of the compounds on B16F10Nex2 cells. The most active compound 1 induced cytotoxic effects on tumor cells, with IC50 values of 18.3, 52.1, and 58.9 mu M against HL-60, HeLa, and B16F10-Nex2 tumor cells, respectively. Furthermore, it was observed in melanoma cells that compound 1 induced several specific apoptotic hallmarks, such as morphological changes in the cell shape structure, nuclear DNA condensation, specific chromatin fragmentation, and disruption in the mitochondrial membrane potential, which are related to the intrinsic apoptotic pathway. (AU)

• Processo FAPESP: 14/08961-2 - Identificação química e avaliação do potencial antitumoral dos metabólitos especiais de Guarea macrophylla ssp. tuberculata (Meliaceae)
• Beneficiário: Geanne Alexsandra Alves Conserva
• Modalidade de apoio: Bolsas no Brasil - Mestrado