2,4-Dichlorobenzyl thiocyanate, an antimitotic agent that alters microtubule morphology.
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.
Abraham
I
I
Dion
R L
RL
Chi
D M
DM
Gottesman
M M
MM
Hamel
E
E
D002460:Cell Line; D004351:Drug Resistance; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects*; D011108:Polymers / Q000378:metabolism; D013329:Structure-Activity Relationship; D013861:Thiocyanates / Q000378:metabolism / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism
D011108:Polymers; D013861:Thiocyanates; D014404:Tubulin; C050043:2,4-dichlorobenzyl thiocyanate