Selective cytotoxicity of Pancratistatin-related natural Amaryllidaceae alkaloids: evaluation of the activity of two new compounds

Abstract

Background: Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the Cring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substuituted crinane skeleton.

Sinalização celular para apoptose em linhagem celular de adenocarcinoma (MCF-7) e carcinoma ductal invasivo de mama (ZR 7531) tratados com alcalódes isolados de Pterogyne nitens

“…We assumed the hypothesis that caspase 3/7 activity can be evaluated at lower concentrations as function of cell damages, which are not yet totally understood [32][33] Guanidine alkaloids form a rare group of natural products. Although most chemical studies on plant alkaloids show they have phenolic groups in common [34][35] the trisubstituted alkaloid, which was demonstrated to be highly deleterious to the cell lines [35][36]. Comparing the cytotoxicity of the two alkaloids, we observed greater activity in PGD than in PGN, due to the lower IC 50 of the former.…”

“…Pelo fato de muitos medicamentos utilizados no tratamento para câncer apresentarem estrutura semelhante ao de um alcalóide, atualmente estão isolando alcalóides de herbáceos nunca antes estudados para verificar os seus possíveis efeitos sobre a doença . Embora a maioria dos estudos com alcalóides tenha como característica química comum grupamentos fenólicos (MCNULTY et al, 2007;GRIFFIN et al, 2007) (BAO et al, 2004;DASSONNEVILLE et. al., 2000).…”

“…A Citometria de fluxo é um método qualitativo, quantitativo e exato para análise de apoptose (CHINKWO, 2005;BERTHO et al, 2000), porém o ensaio não distingue a apoptose tardia da necrose, pois o método avalia a apoptose pela translocação da fosfotidilserina para a membrana externa fosfolipídica (GRIFFIN et al, 2007;RÜCKER-MARTIN et al, 1999). Entretanto, a avaliação de apoptose por esse método não permite determinar os diferentes estágios de apoptose, denominados precoce e tardia (PEC et al, 2003;BOERSMA et al, 2005).…”

Alkaloids extracted from Pterogyne nitens induce apoptosis in malignant breast cell line

“…We assumed the hypothesis that caspase 3/7 activity can be evaluated at lower concentrations as function of cell damages, which are not yet totally understood [33,34] Guanidine alkaloids form a rare group of natural products. Although most chemical studies on plant alkaloids show they have phenolic groups in common [35,36], PGN and PGD isolated from P. nitens are unusual alkaloids. Their chemical structures bear disubstituted guanidine moiety.…”

Effect of erythrinaline alkaloids from Erythrina lysistemon on human recombinant caspase-3

“…Activation of caspase-3 may be a critical therapeutic target for prostate cancer treatment. Alkaloids activate cellular caspase-3-like activity and up-regulate expression of caspase-3 in various cancer cell lines (Fil'chenkov et al, 2006;Ganguly and Khar, 2002;Deng et al, 2006;Ito et al, 2006;Griffin et al, 2007;Griffin et al, 2011). To the best of our knowledge, the direct effect of alkaloids on human recombinant caspase-3 has not been reported, though the effect of alkaloids on prostate cancer cell lines (e.g.…”