Elmeligie Salwa, Khalil Nadia A, Ahmed Eman M, Emam Soha H
Faculty of Pharmacy, Department of Pharmaceutical Organic Chemistry, Cairo University, Cairo, Egypt.
Arch Pharm (Weinheim). 2017 Feb;350(2). doi: 10.1002/ardp.201600256. Epub 2017 Feb 2.
A series of new pyridine derivatives 4a-c, 5a-d, 6a-d, 7a-f, and 8a-f structurally related to ABT-751 were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were tested for their cytotoxic activity in vitro against the HCT-116 and HepG-2 cancer cell lines using the MTT assay. The results showed that compound 8d has higher cytotoxic activity than the reference antimitotic agent colchicine, against both tested cell lines, with IC = 0.52 and 1.40 μM, respectively. The three most active compounds, 5d, 8b, and 8d, were further screened in vitro for inhibition of tubulin and showed remarkable results in comparison to colchicine.
合成了一系列与ABT-751结构相关的新型吡啶衍生物4a-c、5a-d、6a-d、7a-f和8a-f，并通过光谱手段和元素分析对其进行了表征。使用MTT法对所有合成化合物进行了体外抗HCT-116和HepG-2癌细胞系的细胞毒性活性测试。结果表明，化合物8d对两种测试细胞系的细胞毒性活性均高于参考抗有丝分裂剂秋水仙碱，其IC50分别为0.52和1.40μM。进一步对三种活性最高的化合物5d、8b和8d进行了体外微管蛋白抑制筛选，与秋水仙碱相比显示出显著结果。
