当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > 2,4-Dichlorobenzyl thiocyanate, an antimitotic agent that alters microtubule morphology.

2,4-Dichlorobenzyl thiocyanate, an antimitotic agent that alters microtubule morphology.

Abstract：

:A compound of simple structure, 2,4-dichlorobenzyl thiocyanate (DCBT), is an antimitotic agent with a number of unusual properties. The drug causes an extreme reorganization of microtubules in cells in culture. Most normal microtubules disappear, and remaining tubulin-containing structures appear to be bundled or aggregated. DCBT irreversibly inhibits in vitro polymerization of purified tubulin, but only after a prolonged preincubation of the protein with the drug. Binding of radiolabeled DCBT to tubulin similarly requires a long incubation time, with the reaction not being complete even after 6 hr at 37 degrees C. A specific interaction with tubulin is also shown by the crossresistance to DCBT of Colcemid-resistant cells with an altered beta-tubulin. A human KB carcinoma cell line and a Chinese hamster ovary cell line selected for crossresistance to multiple chemotherapeutic agents, including most antimitotic drugs, are sensitive to DCBT. Initial structure-function studies have demonstrated weak antimitotic and antitubulin activity with the parent compound benzyl thiocyanate. Chlorination at either position 2 or position 4 of the phenyl ring produces compounds of intermediate activity (4-chlorobenzyl thiocyanate is more active than 2-chlorobenzyl thiocyanate). The thiocyanate moiety appears to be essential for activity.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Abraham I,Dion RL,Chi DM,Gottesman MM,Hamel E

doi

10.1073/pnas.83.18.6839

subject

Has Abstract

pub_date

1986-09-01 00:00:00

pages

6839-43

issue

18

eissn

0027-8424

issn

1091-6490

journal_volume

83

pub_type

杂志文章

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