Mohareb Rafat Milad, Megally Abdo Nadia Youssef
Chemistry Department, Faculty of Science, Cairo University.
Chem Pharm Bull (Tokyo). 2015;63(9):678-87. doi: 10.1248/cpb.c15-00115.
A series of coumarin analogues bearing 4H-pyran rings 2a-d, 11a-d and 1,4-dihydropyridine rings 3a-d, 12a-d at position 3 were synthesized starting from either 3-acetyl coumarin (1) or the coumarin acetohydrazide derivative 4. Condensation of 3-acetylcoumarin (1) with 2-cyanoacetohydrazide afforded 2-cyano-N'-{1-[2-oxo-2H-chromen-3-yl]ethylidene}acetohydrazide (4). Reaction of compound 4 with elemental sulfur and either malononitrile or ethyl cyanoacetate afforded the thiophene derivatives 8 and 9, respectively. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All synthesized compounds were screened for their in vitro anticancer activity against six human cancer cell lines and normal fibroblasts. Several compounds showed potent inhibition with an IC50 value of ˂870 nM. Compound 3d exhibited equivalent cytotoxic effect as the standard CHS 828 against a breast cancer cell line (IC50 value=18 nM). Normal fibroblast cells (WI38) were affected to a much lesser extent (IC50 value >10000 nM).
从3-乙酰基香豆素（1）或香豆素乙酰肼衍生物4出发，合成了一系列在3位带有4H-吡喃环2a-d、11a-d和1,4-二氢吡啶环3a-d、12a-d的香豆素类似物。3-乙酰基香豆素（1）与2-氰基乙酰肼缩合得到2-氰基-N'-{1-[2-氧代-2H-色烯-3-基]亚乙基}乙酰肼（4）。化合物4与元素硫以及丙二腈或氰基乙酸乙酯反应，分别得到噻吩衍生物8和9。根据新合成化合物的光谱数据和元素分析确定了其结构。对所有合成化合物针对六种人类癌细胞系和正常成纤维细胞进行了体外抗癌活性筛选。几种化合物表现出强效抑制作用，IC50值＜870 nM。化合物3d对乳腺癌细胞系表现出与标准品CHS 828相当的细胞毒性作用（IC50值 = 18 nM）。正常成纤维细胞（WI38）受到的影响要小得多（IC50值＞10000 nM）。
