Lead identification of conformationally restricted benzoxepin type combretastatin analogs: synthesis, antiproliferative activity, and tubulin effects

被引：16

作者：

Barrett, Irene ^{[1
]}

Carr, Miriam ^{[1
]}

O'Boyle, Niamh ^{[1
]}

Greene, Lisa M.

Knox, Andrew J. S. ^{[2
]}

Lloyd, David G. ^{[2
]}

Zisterer, Daniela M.

Meegan, Mary J. ^{[1
]}

机构：

[1] Trinity Coll Dublin, Sch Pharm & Pharmaceut Sci, Ctr Synth & Chem Biol, Dublin 2, Ireland

[2] Trinity Coll Dublin, Sch Biochem & Immunol, Mol Design Grp, Dublin 2, Ireland

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2010年 / 25卷 / 02期

关键词：

Benzoxepin; combretastatin analogs; antiproliferative activity; ANTINEOPLASTIC AGENTS; BINDING-SITE; BIOLOGICAL EVALUATION; CYTOTOXIC EVALUATION; ESTROGEN-RECEPTOR; ANTICANCER DRUGS; ANTITUMOR AGENTS; TAXOL BINDING; A-4; ANALOGS; POLYMERIZATION;

D O I：

10.3109/14756360903169659

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We have synthesized a series of polymethoxylated rigid analogs of combretastatin A-4 which contain a benzoxepin ring in place of the usual ethylene bridge present in the natural combretastatin products. The compounds display antiproliferative activity when evaluated against the MCF-7 and MDA human breast carcinoma cell lines. 5-(3-Hydroxy-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-2,3-dihydro-benzoxepine (11g) was found to be the most potent product when evaluated against the MCF-7 breast cancer cell line. A brief computational study of the structure-activity relationship for the synthesized compounds is presented. These 4,5-diarylbenzoxepins are identified as potentially useful scaffolds for the further development of antitumor agents which target tubulin.

引用

页码：180 / 194

页数：15

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