518-15-0Relevant academic research and scientific papers
A Novel Synthesis of Colchicide and Analogues from Thiocolchicine and Congeners: Reevaluation of Colchicide as a Potential Antitumor Agent
Dumont, Raymond,Brossi, Arnold,Chignell, Colin F.,Quinn, Frank R.,Suffness, Matthew
, p. 732 - 735 (1987)
Desulfurization of thiocolchicine with Raney nickel in a hydrogen atmosphere yielded tetrahydromethoxycolchicine (2), which was readily separated from unreacted thiocolchicine by chromatography and was smoothly oxidized to 10-demethoxycolchicine (colchicide) by Pd/C in refluxing toluene.Several analogues of colchicide were prepared from the corresponding thiocolchicines by this procedure.Treatment of colchicide with concentrated sulfuric acid yielded 2-demethylcolchicide.Colchicide and its analogues were found to be inactive in a tubulin-binding assay.Evidence is presented that colchicide prepared earlier from thiocolchicine with Raney nickel in aerial atmosphere was contamination with 1-2percent thiocolchicine.
Colchicine red-ox chemistry revisited: Cathodic behavior and EPR observation of an intermediate radical anion
Cavazza, Marino,Nucci, Lamberto,Pannocchia, Elisa,Pardi, Lucio,Pergola, Francesco,Pinzino, Calogero,Pietra, Francesco
, p. 11601 - 11608 (2007/10/03)
Colchicine (1), a potently antimitotic alkaloid and useful laboratory tool in cancer research, undergoes cathodic reduction in DMF forming an ESR- observable radical anion (1r) which is characterized by the isotropic hyperfine coupling constants 8.9, 4.3, 0.75, 0.49 and 0.48 G for H-8, H-12, OCH3, H-11 and H-4, respectively, and a much flattened troponoid ring. Assignments are aided by selective deuteriation of colchicine at C-8, C-11 and COCH3, as well as by spectral simulation and ab initio calculations of electron spin densities. Whether the colchicine radical anion may exist in nature is also discussed.
Synthesis and Tubulin Binding of Novel C-10 Analogues of Colchicine
Staretz, Marianne E.,Hastie, Susan Bane
, p. 758 - 764 (2007/10/02)
A series of novel C-10 derivatives of colchicine have been prepared and evaluated for inhibition of in vitro microtubule assembly and of colchicine binding to tubulin.The C-10 substituent of colchicine was replaced by halogens, alkyl and alkoxy groups, and hydrogen.Many of these compounds are available by nucleophilic substitution of 10-fluoro-10-demethoxycolchicine (9) without concomitant formation of ring contraction products.Compound 9 is prepared by reaction of (diethylamino)sulfur trifluoride with colchicine.Unlike most reactions of colchicine, the colchicine rather than the isocolchicine regioisomer is the predominant product of this reaction.It was found that modification of the C-10 substituent of colchicine had a relatively minor effect on the potency of the colchicinoids.The electronic nature of the substituent had no significant effect on the efficacy of the compound, indicating that hydrogen bonding or polar interactions between the C-10 substituent of colchicinoids and an amino acid in the colchicine binding site on tubulin are not present in the colchicine-tubulin complex.A decrease in activity was observed with increasing length of the alkyl chain bonded to the C-10 position, but potency was less affected when the alkyl groups were positioned in close proximity to the C-10 carbon of the tropone ring.It is concluded that the steric rather than the electronic properties of the C-10 substituent are the predominant determinants of activity in this series.
