Collect. Czech. Chem. Commun.
1991, 56, 2306-2312
https://doi.org/10.1135/cccc19912306
Synthesis and tubulin interaction of thiocolchicines containing an isothiocyanato group. Synthesis of C(2)-deuterated and C(2)-14C-labeled 7-isothiocyanatodeacetamidothiocolchicine
Anjum Muzaffara, Ernest Hamelb, Rouli Baib and Arnold Brossia
a Natural Products Section, Laboratory of Structural Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, U.S.A.
b Laboratory of Molecular Pharmacology Development Therapeutics Program, Division of Cancer Treatment, NCI, National Institutes of Health, Bethesda, Maryland 20892, U.S.A.
Abstract
Synthesis of isothiocyanato substituted thiocolchicines XI - XIV is described. Introduction of an isotope label is demonstrated with the deuterated isothiocyanate XII and the 14C-labeled analog XIII. These isothiocyanates inhibit tubulin polymerization at low concentration. In addition, the 14C-labeled XIII forms covalent bond(s) with tubulin. Unfortunately, the covalent reaction while rapid, is not inhibited by preincubation of tubulin with colchicine. The covalent interaction of XIII with tubulin thus appears to be nonspecific, limiting its use as a marker of the colchicine binding site on tubulin.
