Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology (Council of Scientific and Industrial Research), Hyderabad 500607, India.
Eur J Med Chem. 2013 Feb;60:305-24. doi: 10.1016/j.ejmech.2012.12.008. Epub 2012 Dec 20.
Two new series of compounds E-2,3,4-trimethoxy-6-styrylbiphenyls and 2,3,4-trimethoxy-6-(1-phenylvinyl)biphenyls were designed, synthesized and evaluated for antitubulin activity. A common intermediate 4,5,6-trimethoxybiphenyl-2-carbaldehydes was employed to generate the two scaffolds. Majority of the analogs inhibited cell proliferation and those functionalized with 3,4-(1,3-dioxolane) and 3,4-difluoro groups were identified as effective inhibitors in both the series. Treatments with 19b, 19c, 22b and 22c arrested cells at G2/M phase, disrupted microtubule network, accumulated tubulin in the soluble fraction and manifested an increased expression of the G2/M marker, Cyclin B1. Molecular docking analysis demonstrated the interaction of these compounds at the colchicine binding site of tubulin.
两个新系列的化合物 E-2,3,4-三甲氧基-6-苯乙烯基联苯和 2,3,4-三甲氧基-6-(1-苯乙烯基)联苯被设计、合成并评估了它们的抗微管蛋白活性。一个共同的中间体 4,5,6-三甲氧基联苯-2-甲酰被用来生成这两个支架。大多数类似物抑制细胞增殖，其中 3,4-(1,3-二氧戊环)和 3,4-二氟取代的类似物被鉴定为这两个系列中的有效抑制剂。用 19b、19c、22b 和 22c 处理可使细胞停滞在 G2/M 期，破坏微管网络，使微管蛋白在可溶部分积累，并表现出 G2/M 标志物 Cyclin B1 的表达增加。分子对接分析表明，这些化合物在微管蛋白的秋水仙碱结合部位相互作用。
