抗癌β-内酰胺类药物的合成：作用机制

Synthesis of anticancer beta-lactams: mechanism of action.

作者信息

Banik Bimal K, Becker Frederick F, Banik Indrani

机构信息

The University of Texas M.D. Anderson Cancer Center, Department of Molecular Pathology, Unit 89, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

出版信息

Bioorg Med Chem. 2004 May 15;12(10):2523-8. doi: 10.1016/j.bmc.2004.03.033.

DOI:10.1016/j.bmc.2004.03.033

PMID:15110834

Abstract

Synthesis of the trans 1-N-chrysenyl and 1-N-phenanthrenyl 3-acetoxy-4-phenyl-2-azetidinones has been achieved. Microwave-assisted reaction has proved useful in the synthesis of these compounds. Cell growth inhibition study has indicated selective anticancer activity against two leukemia and colon carcinoma cell lines. A mechanistic correlation of their anticancer activity has been described. Striking G2 blockade that is clearly distinct in cell cycle analysis and demonstrated only in sensitive cell lines has been observed. They do not induce apoptosis in sensitive or resistant lines. They also do not inhibit topoisomerases. Ames test has shown they are nonmutagenic.

摘要

已成功合成反式1-N- Chrys烯基和1-N-菲基3-乙酰氧基-4-苯基-2-氮杂环丁酮。微波辅助反应已证明对这些化合物的合成有用。细胞生长抑制研究表明对两种白血病和结肠癌细胞系具有选择性抗癌活性。已描述了它们抗癌活性的机制相关性。在细胞周期分析中观察到明显不同且仅在敏感细胞系中出现的显著G2期阻滞。它们在敏感或耐药细胞系中均不诱导凋亡。它们也不抑制拓扑异构酶。艾姆斯试验表明它们无致突变性。