Tormo José R, Royo Inmaculada, Gallardo Teresa, Zafra-Polo M Carmen, Hernández Pilar, Cortes Diego, Peláez Fernando
CIBE-Merck Research Laboratories, Merck, Sharp & Dohme de España S.A., C/Josefa Valcárcel, 38, Madrid 28027, Spain.
Oncol Res. 2003;14(3):147-54. doi: 10.3727/000000003771013099.
In this study we evaluated a mono-tetrahydrofuranic subgroup of natural acetogenins that had shown in previous enzyme inhibition studies different potency trends compared with the bis-tetrahydrofuranic acetogenin subgroup. The compounds were tested against colon, breast, lung, liver, and ovarian tumor cell lines. A drug-resistant ovarian cell line was also included in the panel. In general the compounds were more potent than doxorubicin. The goal was to determine how well the mitochondrial complex I inhibition correlates with the in vitro antitumor potency of these natural mono-tetrahydrofuranic acetogenins and of some derivatives. The results indicate that both the reduction of the terminal gamma-lactone after its translactonization and the introduction of an hydroxylimine group in the alkyl chain, near the mono-tetrahydrofuranic moiety, increased the antitumor activity, even against the doxorubicin-resistant cell line.
在本研究中，我们评估了天然产乙酸素的单四氢呋喃亚组，该亚组在先前的酶抑制研究中显示出与双四氢呋喃产乙酸素亚组不同的效价趋势。这些化合物针对结肠、乳腺、肺、肝和卵巢肿瘤细胞系进行了测试。该细胞系组中还包括一个耐药卵巢细胞系。总体而言，这些化合物比阿霉素更有效。目的是确定线粒体复合物I抑制与这些天然单四氢呋喃产乙酸素及其某些衍生物的体外抗肿瘤效价之间的关联程度。结果表明，末端γ-内酯在转内酯化后还原，以及在靠近单四氢呋喃部分的烷基链中引入羟基亚氨基，均提高了抗肿瘤活性，甚至对阿霉素耐药细胞系也有活性。
