Abdelrahman Mostafa H, Aboraia Ahmed S, Youssif Bahaa G M, Elsadek Bakheet E M
Department of Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Chem Biol Drug Des. 2017 Jul;90(1):64-82. doi: 10.1111/cbdd.12928. Epub 2017 Jan 31.
Novel 3-alkoxymethyl/3-phenyl indole-2-carboxamide derivatives were synthesized and evaluated for their anticancer activity. Most of the tested compounds showed moderate to excellent activity against the tested cell lines (MCF7 and HCT116). 3-Phenyl substitution on indole with p-piperidinyl phenethyl 24a and p-dimethylamino phenethyl 24c exhibited anticancer activity against MCF7 with IC of 0.13 and 0.14 μm, respectively. Further mechanistic study of the most active compounds through their action on cell cycle showed disturbance in cell cycle progression and cell cycle arrest. For future development of this series of compounds, pharmacophore study was conducted which indicated that the enhancement of the activity could be achieved through the addition of acceptor or donating groups to the already-present indole nucleus.
合成了新型3-烷氧基甲基/3-苯基吲哚-2-甲酰胺衍生物，并对其抗癌活性进行了评估。大多数测试化合物对测试细胞系（MCF7和HCT116）表现出中度至优异的活性。吲哚上的3-苯基被对哌啶基苯乙基24a和对二甲氨基苯乙基24c取代后，对MCF7显示出抗癌活性，IC50分别为0.13和0.14μm。通过对最具活性的化合物作用于细胞周期的进一步机制研究表明，细胞周期进程受到干扰且细胞周期停滞。为了该系列化合物的未来开发，进行了药效团研究，结果表明通过向已有的吲哚核添加受体或供体基团可以实现活性增强。
