Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia.
Department of Chemistry, Faculty of Science, Mansura University, Mansura 35516, Egypt.
Molecules. 2019 Apr 4;24(7):1332. doi: 10.3390/molecules24071332.
An efficient and practical method for the synthesis of 2,6-diaryl-4-oxo-,'-di(pyridin-2-yl)cyclohexane-1,1-dicarboxamide is described in this present study, which occurs through a double Michael addition reaction between diamide and various dibenzalacetones. The reaction was carried out in dichloromethane (DCM) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The anticancer activities of the synthesized compounds were evaluated in several cancer cell lines, including MCF-7, MDA-MB-231, SAS, PC-3, HCT-116, HuH-7 and HepG2 cells. From these experiments, we determined that MDA-MB-231 was the most sensitive cancer cell line to the compounds , , , and , which exhibited variable anticancer activities ( [IC = 5 ± 0.25 µM] > 3e [IC = 5 ± 0.5 µM] > [IC = 7 ± 1.12 µM] > [IC = 18 ± 0.87 µM] > [IC = 45 ± 3 µM]). Of these, (substituted -trifluoromethylphenyl and chloropyridine) showed good potency (IC = 6 ± 0.78 µM) against HCT-116 colorectal cancer cells and exhibited high toxicity against HuH-7 liver cancer cells (IC = 4.5 ± 0.3 µM). These values were three times higher than the values reported for cisplatin (IC of 8 ± 0.76 and 14.7 ± 0.5 µM against HCT-116 and HuH-7 cells, respectively). The highest α-glucosidase inhibitory activity was detected for the , and compounds. The details of the binding mode of the active compounds were clarified by molecular docking studies.
本研究描述了一种高效实用的 2,6-二芳基-4-氧代-,'-二(吡啶-2-基)环己烷-1,1-二羧酸酰胺的合成方法，该方法通过双迈克尔加成反应在二氯甲烷（DCM）中进行，使用 1,8-二氮杂二环[5.4.0]十一-7-烯（DBU）作为催化剂。合成化合物的抗癌活性在多种癌细胞系中进行了评估，包括 MCF-7、MDA-MB-231、SAS、PC-3、HCT-116、HuH-7 和 HepG2 细胞。从这些实验中，我们确定 MDA-MB-231 是对化合物 、 、 、 和 最敏感的癌细胞系，这些化合物表现出不同的抗癌活性（[IC = 5 ± 0.25 µM] > 3e [IC = 5 ± 0.5 µM] > [IC = 7 ± 1.12 µM] > [IC = 18 ± 0.87 µM] > [IC = 45 ± 3 µM]）。其中， （取代 -三氟甲基苯基和氯吡啶）对 HCT-116 结肠癌细胞具有良好的活性（IC = 6 ± 0.78 µM），对 HuH-7 肝癌细胞表现出高毒性（IC = 4.5 ± 0.3 µM）。这些值是顺铂（IC 分别为 8 ± 0.76 和 14.7 ± 0.5 µM）的三倍。对 、 、 化合物的α-葡萄糖苷酶抑制活性最高。通过分子对接研究阐明了活性化合物的结合模式的详细信息。
