Antitumor agents--CLXXV. Anti-tubulin action of (+)-thiocolchicine prepared by partial synthesis.

Abstract

(+)-Thiocolchicine (2b) was prepared from (+/-)-colchicine (1) in a five-step reaction sequence that included chromatographic separation of appropriate camphanylated diastereomers. Acid hydrolysis of the (+)-diastereomer, followed by acetylation, yielded the desired product 2b. (+)-Thiocolchicine has 15-fold lower inhibitory activity against tubulin polymerization than (-)-thiocolchicine, and is 29-fold less potent for inhibiting growth of human Burkitt lymphoma cells. The enantiomer 2a, prepared from the (-)-camphanylated diastereomer, had potent activity in all assays comparable to that of (-)-thiocolchicine prepared by other methods. These results support the hypothesis that the proper configuration of colchicine-related compounds is an important requirement for their anti-tubulin action.

• Authors: Q Shi, P Verdier-Pinard, A Brossi, E Hamel, K H Lee
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 5 Issue 12 Pg. 2277-82 (Dec 1997) ISSN: 0968-0896 [Print] England
• PMID: 9459025 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Tubulin Modulators
• thiocholchicine
• Colchicine

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Chromatography, Thin Layer
• Colchicine (analogs & derivatives, chemical synthesis, pharmacology)
• Humans
• Isomerism
• Magnetic Resonance Spectroscopy
• Models, Chemical
• Tubulin Modulators
• Tumor Cells, Cultured