HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.
AuthorsI Abraham, R L Dion, D M Chi, M M Gottesman, E Hamel
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 83 Issue 18 Pg. 6839-43 (Sep 1986) ISSN: 0027-8424 [Print] United States
PMID3462730 (Publication Type: Journal Article)
Chemical References
  • Polymers
  • Thiocyanates
  • Tubulin
  • 2,4-dichlorobenzyl thiocyanate
Topics
  • Cell Line
  • Drug Resistance
  • Humans
  • Microtubules (drug effects)
  • Mitosis (drug effects)
  • Polymers (metabolism)
  • Structure-Activity Relationship
  • Thiocyanates (metabolism, pharmacology)
  • Tubulin (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: