Convergent synthesis and biological evaluation of 2-amino-4-(3',4',5'-trimethoxyphenyl)-5-aryl thiazoles as microtubule targeting agents.
Convergent synthesis and biological evaluation of 2-amino-4-(3',4',5'-trimethoxyphenyl)-5-aryl thiazoles as microtubule targeting agents.
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DOI：
10.1021/jm200392p
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发表时间：
2011-07-28
影响因子：
7.3
通讯作者：
Viola, Giampietro
中科院分区：
文献类型：
--
作者：
Romagnoli, Romeo;Baraldi, Pier Giovanni;Brancale, Andrea;Ricci, Antonio;Hamel, Ernest;Bortolozzi, Roberta;Basso, Giuseppe;Viola, Giampietro
考布他汀A-4是一种有效的微管蛋白聚合抑制剂，我们合成了一系列新的2-氨基-4-（3′，4 ′，5 ′-三甲氧基苯基）-5-芳基噻唑类化合物，目的是评价噻唑骨架5-位苯基上取代基对生物活性的影响。对位的乙氧基产生了系列中最具活性的化合物，对七种癌细胞系中的五种的IC 50值为0.03-0.9 nM。活性最高的化合物在多药耐药癌细胞中保留了全部活性，并通过微管蛋白的秋水仙碱位点发挥作用。经处理的细胞被阻滞在细胞周期的G2/M期，细胞死亡通过仅部分依赖于半胱天冬酶的凋亡途径进行。初步结果表明，除了细胞凋亡导致的细胞死亡外，细胞也通过有丝分裂灾难作为替代细胞死亡机制而被杀死。
Combretastatin A-4, a potent tubulin polymerization inhibitor, caused us to synthesize a novel series of 2-amino-4-(3′,4′,5′-trimethoxyphenyl)-5-aryl thiazoles with the goal of evaluating the effects of substituents on the phenyl at the 5-position of the thiazole skeleton on biological activities. An ethoxy group at the para-position produced the most active compound in the series, with IC50 values of 0.03–0.9 nM against five of seven cancer cell lines. The most active compounds retained full activity in multidrug resistant cancer cells and acted through the colchicine site of tubulin. Treated cells were arrested in the G2/M phase of the cell cycle, with cell death proceeding through an apoptotic pathway that was only partially caspase-dependent. Preliminary results suggest that, in addition to cell death by apoptosis, cells were also killed via mitotic catastrophe as an alternative cell death mechanism.
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影响因子：
4.7
作者：
Cooney, Matthew M;Ortiz, Jose;Remick, Scot C
通讯作者：
Remick, Scot C
影响因子：
7.2
作者：
Cenciarelli, Chiara;Tanzarella, Caterina;Antoccia, Antonio
通讯作者：
Antoccia, Antonio
影响因子：
3.2
作者：
Gaukroger, K;Hadfield, JA;McGown, AT
通讯作者：
McGown, AT
影响因子：
4.8
作者：
Cai, JY;Jones, DP
通讯作者：
Jones, DP
影响因子：
7.3
作者：
Bonezzi, Katiuscia;Taraboletti, Giulia;Giavazzi, Raffaella
通讯作者：
Giavazzi, Raffaella