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Synthesis and biological evaluation of 1,1-dichloro-2,3-diarylcyclopropanes as antitubulin and anti-breast cancer agents.

Abstract：

:Z-1,1-Dichloro-2,3-diphenylcyclopropane (1) is an effective anti-breast cancer agent in rodents and in cell culture. We recently determined that 1 inhibits tubulin assembly in vitro and causes microtubule loss in breast cancer cells, leading to accumulation in the G2/M portion of the cell cycle. Aryl ring-halogenated, methoxylated and benzyloxylated derivatives of 1, as well as its E-isomer and the dichlorocyclopropyl derivative of diethylstilbestrol (DES), were synthesized and tested for their ability to inhibit, the assembly of tubulin into microtubules. Including 1, 17 cyclopropyl compounds were tested. One (Z-1,1-dichloro-2-(4-methoxyphenyl)-3-phenylcyclopropane (12)) was found to be more active than 1. In addition, E-1,1-dichlorocyclopropylDES (17) was more potent than DES. The E-isomer of 1 (16) was inactive. The cytostatic activities of the compounds against MCF-7 and MDA-MB231 human breast cancer cells, and their abilities to perturb microtubules in MCF-7 cells were also evaluated. Z-Dichloro-2-(4-fluorophenyl)-3-phenylcyclopropane (5), Z-1,1-dichloro-2-(4-fluorophenyl)-3-(4-methoxyphenyl)cyclopropane (11), and Z-1,1-dichloro-2-(4-methoxyphenyl)-3-phenylcyclopropane (12) were more potent than 1 against the breast cancer cells.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Jonnalagadda SS,ter Haar E,Hamel E,Lin CM,Magarian RA,Day BW

doi

10.1016/s0968-0896(97)00014-x

subject

Has Abstract

pub_date

1997-04-01 00:00:00

pages

715-22

issue

4

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(97)00014-X

journal_volume

5

pub_type

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