Hamon N W, Bassendowski D L, Wright D E, Dimmock J R, Noble L M
J Pharm Sci. 1978 Nov;67(11):1539-42. doi: 10.1002/jps.2600671112.
Five cytotoxic Mannich bases (5-dimethylamino-1-substituted phenyl-1-penten-3-ones), three having antineoplastic activity, were evaluated for respiratory-inhibiting properties in rat liver mitochondria in the presence of four substrates: succinate, glutamate, 3-hydroxybutyrate, and palmitylcarnitine. Four compounds (Ib--Ie) showed significant inhibiting properties which, on occasion, were reversed partially by coenzyme Q10. Evaluation of the spectra of the mitochondrial cytochromes indicated that Ib--Ie blocked the electron transport chain prior to the sequence of cytochromes. Since inhibition occurred when different substrates were used, a common site of action for Ib--Ie is likely; competition of Ib--Ie with coenzyme Q10 probably occurs. Compounds Ia--Ie inhibited RNA polymerase from Swiss mouse kidney cells but were virtually bereft of activity versus RNA polymerase from L-1210 leukemia cells. Polarography of the Mannich bases and the related styryl ketones showed that antineoplastic activity was associated with higher half-wave potentials.
对5种细胞毒性曼尼希碱（5 - 二甲基氨基 - 1 - 取代苯基 - 1 - 戊烯 - 3 - 酮）进行了评估，其中3种具有抗肿瘤活性，在存在琥珀酸、谷氨酸、3 - 羟基丁酸和棕榈酰肉碱4种底物的情况下，研究它们对大鼠肝线粒体呼吸抑制的特性。4种化合物（Ib - Ie）表现出显著的抑制特性，某些情况下，辅酶Q10可部分逆转这种抑制作用。对线粒体细胞色素光谱的评估表明，Ib - Ie在细胞色素序列之前阻断了电子传递链。由于使用不同底物时均出现抑制作用，Ib - Ie可能存在共同的作用位点；Ib - Ie与辅酶Q10可能存在竞争。化合物Ia - Ie抑制瑞士小鼠肾细胞的RNA聚合酶，但对L - 1210白血病细胞的RNA聚合酶几乎没有活性。曼尼希碱和相关苯乙烯基酮的极谱分析表明，抗肿瘤活性与较高的半波电位有关。
