Aly Mohamed R E, Ibrahim El-Sayed I, El Shahed Fakher A, Soliman Hamdy A, Ibrahim Zein S, El-Shazly Samir A M
Chemistry Department, Faculty of Science, Taif University, Taif, Alhawyia, Kingdom of Saudi Arabia.
Bioorg Khim. 2012 Jul-Aug;38(4):489-95. doi: 10.1134/s1068162012030119.
Two derivatives of 2-(4-acetylanilino)quinolines (IIIa, b) were synthesized as scaffolds for synthesis of open chalcone analogues (Va-f) through Claisen-Schmidt condensation with a set of aromatic aldehydes (IVa-d). Derivatives (Va, b) were further manipulated into cyclic alpha,beta-unsaturated ketones by Michael-addition of acetylacetone and ethylacetoacetate affording derivatives (VI-VII). Deethoxycarboxylation of derivatives (VIIa, b) afforded cyclohexenons (VIIIa, b) allowing formation of a mini library of alpha,beta-unsaturated ketones for screening their anticancer and synergistic anticancer effect with doxorubicin using colon cancer cell line (Caco-2). Two open enones, (Vb) and (Ve), showed significant anticancer activity with IC50 of 5.0 and 2.5 microM respectively. Only one cyclic enone, (VIa) showed synergistic anticancer activity with doxorubicin at 10 microM.
合成了两种2-(4-乙酰苯胺基)喹啉衍生物(IIIa, b)，作为通过与一组芳香醛(IVa-d)进行克莱森-施密特缩合反应合成开链查尔酮类似物(Va-f)的骨架。通过乙酰丙酮和乙酰乙酸乙酯的迈克尔加成反应，将衍生物(Va, b)进一步转化为环状α,β-不饱和酮，得到衍生物(VI-VII)。衍生物(VIIa, b)的脱乙氧基羧化反应得到环己烯酮(VIIIa, b)，从而形成了一个α,β-不饱和酮的小型文库，用于使用结肠癌细胞系(Caco-2)筛选它们的抗癌活性以及与阿霉素的协同抗癌作用。两种开链烯酮(Vb)和(Ve)显示出显著的抗癌活性，IC50分别为5.0和2.5微摩尔。只有一种环状烯酮(VIa)在10微摩尔时与阿霉素显示出协同抗癌活性。
