Navegando por Palavras-chave "Atividade citotóxica e apoptose via intrínseca"

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    Identificação química e avaliação do potencial antitumoral dos metabólitos especiais de guarea macrophylla ssp tuberculata (meliaceae)
    (Universidade Federal de São Paulo, 2016-08-24) Conserva, Geanne Alexsandra Alves [UNIFESP]; Lago, João Henrique Ghilardi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Currently, several researches in phytochemical screening are associated with the evaluation of biological activities, aiming the isolation and structural characterization of bioactive compounds. In this context, the species Guarea macrophylla ssp. tuberculata (Meliaceae), unknown in biological point of view, had the ethanol extract of leaves subjected to evaluation of in vitro cytotoxic activity against the B16F10-Nex2 cell lineage. The bioactive extract was subjected to liquid-liquid partition, where the phases in Hexane, EtOAc and DCM were obtained, being the first, the most active (30% cell viability 100 ?g/ml). Aiming the identification of active compounds, the hexane phase of ethanol extract of G. macrophylla was subjected to several chromatographic fractionation techniques fully bio-guided (silica gel 60, Sephadex LH-20, Florisil® and HPLC), allowing then, isolation and structural characterization of two triterpene with cycloartane skeleton: cycloart-23E-ene-3?, 25-diol (I), 23,24-dihydroxy-cicloart-25-en-3-one (II), and two pimarane diterpenes: isopimara -7,15-diene-2?, 3?-diol (III) and isopimara-7,15-diene, 3?-ol (IV). Compounds (II) and (III) are considered unprecedented in the literature, which structures were identified/elucidated by spectroscopic and spectrometric analysis, such as nuclear magnetic resonance (NMR), Infrared (IR), circular dichroism (CD) and spectrometry and high and low resolution mass spectrometry (MS). Isolated compounds were evaluated for their cytotoxic potential by MTT colorimetric quantitative assay against murine melanoma cell lines (B16F10-Nex2) and, against several human tumoral cell lines: human melanoma (A2058), breast adenocarcinoma (MCF7), leukemia (HL-60) and human cervical carcinoma (HeLa), presenting significative IC50 values, ranging from 8,0 ± 0,2 and 94±3.4 µg/mL. But when comparing the IC50 values obtained with the values of the positive control (cisplatin), it can be inferred that the compounds I, II and III performed better just to MCF7 line. Depth studies of cell death mechanism (morphological study, fragmentation and condensation of DNA and measurement of mitochondrial membrane potential) showed that the tumoral cell line, B16F10-Nex2 (murine melanoma), chosen for ongoing work, when treated with I, actives the programmed cell death mechanism (apoptosis), involving the mitochondria as the main affected organelle.