Belal Amany
Pharmaceutical Chemistry Department, College of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; Faculty of Pharmacy, Medicinal Chemistry Department, Beni-Suef University, Beni-Suef, Egypt.
Arch Pharm (Weinheim). 2014 Jul;347(7):515-22. doi: 10.1002/ardp.201400004. Epub 2014 Apr 14.
A novel series of pyrrolo[1,2-a]azepine derivatives 3-7 were synthesized and their structures were confirmed by spectral and elemental analyses. Antitumor activity evaluation of these compounds was carried out against liver (HepG2), breast (MCF7), and colon (HCT116) cancer cell lines using the sulforhodamine-B (SRB) assay method and doxorubicin as reference standard. Compounds 3 and 6 were found to be more potent than doxorubicin against HepG2 cells, with IC50 values of 4, 1.6 and 10.8 nM, respectively. Moreover, compounds 3 and 7 showed broad-spectrum anticancer activity against all the tested cell lines, and their IC50 values were in the nanomolar range (4-44.2 nM and 20.7-45.4 nM, respectively). The 2-benzoylamino derivative of pyrrolo[1,2-a]azepine 5b was the most potent one against MCF7 cells (IC50 of 10.7 nM); however, the 2-(2-chloro-acetylamino)-pyrroloazepine derivative 6 was the most potent against the HCT116 cell line, with an IC50 value of 21.1 nM. The novel compounds were docked into the active site of cyclin-dependent kinase 2 (CDK2) to explore the ability of these compounds to interact with these kinases. All compounds showed a lower binding score energy than the reference ligand.
合成了一系列新型的吡咯并[1,2 - a]氮杂卓衍生物3 - 7，并通过光谱和元素分析确定了它们的结构。使用磺基罗丹明B（SRB）测定法并以阿霉素作为参考标准，对这些化合物针对肝癌（HepG2）、乳腺癌（MCF7）和结肠癌细胞系（HCT116）进行了抗肿瘤活性评估。发现化合物3和6对HepG2细胞的活性比阿霉素更强，IC50值分别为4、1.6和10.8 nM。此外，化合物3和7对所有测试细胞系均显示出广谱抗癌活性，其IC50值在纳摩尔范围内（分别为4 - 44.2 nM和20.7 - 45.4 nM）。吡咯并[1,2 - a]氮杂卓的2 - 苯甲酰氨基衍生物5b对MCF7细胞的活性最强（IC50为10.7 nM）；然而，2 - （2 - 氯乙酰氨基） - 吡咯并氮杂卓衍生物6对HCT116细胞系的活性最强，IC50值为21.1 nM。将这些新型化合物对接至细胞周期蛋白依赖性激酶2（CDK2）的活性位点，以探究这些化合物与这些激酶相互作用的能力。所有化合物的结合评分能量均低于参考配体。
