Carrara Maria, Zampiron Antonella, Barbera Mariagnese, Caputo Anna, Bisi Alessandra, Gobbi Silvia, Belluti Federica, Piazzi Lorna, Rampa Angela, Valenti Piero
Department of Pharmacology and Anaesthesiology, University of Padova, Largo Meneghetti 2, 35131 Padova, Italy.
Anticancer Res. 2005 Mar-Apr;25(2A):1179-85.
Previously, the antitumour activity of some flavone-8-acetic acid (FAA) derivatives substituted with an acid function in position 2 of the benzene ring was evaluated. The most active compound resulted the one bearing a fluorine atom in position 7 of the flavone nucleus. In this paper, we evaluated new mono- or di-fluorinated FAA derivatives.
The cytotoxicity towards two human ovarian adenocarcinoma cell lines, the capability to stimulate human mononuclear cells and murine macrophages' lytic properties were evaluated by MTT. Moreover, the potentiation of lipopolysaccharide (LPS) activity was studied by ELISA analysis of TNF-alpha release.
The analogues showed a direct cytotoxicity comparable to that of 5,6-dimethyl-xanthen-9-one-4-acetic acid (DMXAA), at present in clinical trials. None of the tested compounds was able to stimulate human mononuclear cells' lytic properties after either 4- or 24-h treatment, while after 4-h treatment, the derivative 5a was more able to stimulate murine macrophages with respect to DMXAA. Moreover, a significant increase of 5c and 5d activation was obtained with LPS association, reflected by TNF-alpha production as well.
Like FAA, the new fluorinated derivatives 5a, 5c and 5d showed remarkable activity in murine cells, but this was not confirmed in human models.
此前，对一些在苯环2位被酸官能团取代的黄酮 - 8 - 乙酸（FAA）衍生物的抗肿瘤活性进行了评估。活性最高的化合物是在黄酮核7位带有氟原子的那个。在本文中，我们评估了新的单氟或二氟FAA衍生物。
通过MTT法评估对两种人卵巢腺癌细胞系的细胞毒性、刺激人单核细胞的能力以及小鼠巨噬细胞的裂解特性。此外，通过ELISA分析肿瘤坏死因子 - α（TNF - α）释放来研究脂多糖（LPS）活性的增强情况。
这些类似物显示出与目前正在进行临床试验的5,6 - 二甲基 - 呫吨 - 9 - 酮 - 4 - 乙酸（DMXAA）相当的直接细胞毒性。在4小时或24小时处理后，所测试的化合物均不能刺激人单核细胞的裂解特性，而在4小时处理后，衍生物5a比DMXAA更能刺激小鼠巨噬细胞。此外，与LPS联合使用时，5c和5d的激活显著增加，这也通过TNF - α的产生得到反映。
与FAA一样，新的氟化衍生物5a、5c和5d在鼠细胞中显示出显著活性，但在人体模型中未得到证实。
