1990-46-1Relevant articles and documents
Fluorinated colchicinoids: Antitubulin and cytotoxic properties
Ringel,Jaffe,Alerhand,Boye,Muzaffar,Brossi
, p. 3334 - 3338 (1991)
The synthesis of B-ring and C-ring trifluoroacetamide-substituted colchicinoids and fluoro-substituted colchicineethylamides is presented. The B-ring trifluoroacetamido-substituted analogues exhibit moderate enhancement of potency compared to the nonfluorinated analogues for tubulin assembly inhibition and cytotoxicity toward two wild type cells lines. The C-ring substituted fluoroethylamides have reduced relative potencies in the same systems due to the strong electron-withdrawing effect of the fluoro derivatives. The fluoro colchicinoids are much more cytotoxic toward drug- resistant cell lines than to the wild type cell lines. Their enhanced potency is probably due to an effect of the fluoro moiety on functions specific to resistant cells and/or their higher hydrophobicity that may result in higher intracellular drug content. This finding may suggest the application of designed fluorinated anticancer drugs to overcome acquired resistance which may develop after several regiments of treatment with a nonfluorinated chemotherapeutic agent.
Colchiceine complexes with lithium, sodium and potassium salts-spectroscopic studies
Kurek, Joanna,Barczynski, Piotr
, p. 297 - 308 (2016)
Colchiceine complexes with Li+, Na+ and K+ cations have been synthesized and studied by 1H and 13C NMR, FT-IR, FAB MS and UV-Vis. It has been shown that colchiceine forms stable complexes especially with lithium cation and the most stable structures of the complexes are those in which the acetamide groups are involved in the coordination process. The structures of the colchiceine complexes with Li+, Na+ and K+ cations are discussed in details.
A Facile Synthetic Approach to Nonracemic Substituted Pyrrolo-allocolchicinoids Starting from Natural Colchicine
Shchegravina, Ekaterina S.,Svirshchevskaya, Elena V.,Schmalz, Hans-Günther,Fedorov, Alexey Yu
, p. 1612 - 1622 (2019)
A six-step semisynthetic approach towards chiral nonracemic pyrrolo-allocolchicinoids starting from naturally occurring colchicine was developed. The synthetic scheme includes an electrocyclic tropolone ring contraction to afford allocolchicinic acid followed by the Curtius reaction, giving the corresponding aniline. The Sandmeyer reaction and copper-mediated hydrazination gave hydrazine-substituted allocolchicine. This was introduced into the Fischer indole synthesis, affording libraries of regioisomeric indole-based allocolchicine congeners.
Synthesis and cytostatic properties of polyfunctionalized furanoallocolchicinoids
Gracheva, Iuliia A.,Voitovich, Iuliia V.,Faerman, Vladimir I.,Sitnikov, Nikolay S.,Myrsikova, Ekaterina V.,Schmalz, Hans-Gunther,Svirshevskaya, Elena V.,Fedorov, Alexey Yu
, p. 432 - 443 (2017)
A series of furan-based allocolchicinoids was prepared from commercially available colchicine via a nine-step reaction sequence. Cytostatic activity, cell cycle arrest, apoptosis, tubulin and F-actin expression were studied in vitro in 2D and 3D cultures of normal and tumor epithelial keratinocytes, endothelial and mesenchymal cells. Among the prepared furanoallocolchicine analogues, 14a and 7a displayed the most pronounced anti-cancer activity. These compounds induced two types of effects: (a) cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding (metaphase effect), and (b) pronounced cell stress (as evidenced by the overexpression of tubulin and F-actin), which was caused by the hyperpolarization of mitochondrial and lysosomal membranes (interphase effect).
1-ACETAMIDO-3-(3,4,5-TRIMETHOXYPHENYL)PROPYL.
Yamamoto,Hara Atsushi,Inokawa,Nozoe
, p. 3106 - 3109 (1983)
The treatment of 4- left bracket 1-acetamido-3-(3,4,5-trimethoxyphenyl)propyl right bracket tropolone with etheral diazomethane gave the 6- and 4-substituted title compounds in 51 and 38% yields, respectively. The 270-MHz **1H-NMR spectral analysis performed on these compounds, colchicine, and two methyl ethers of hinokitiol permits unequivocal assignment of the position of the C-substituent on these 2-methoxytropone rings. Attempts were made to effect the direct B-ring closure of these intermediates and 4- left bracket 1-acetamido-3-(3,4,5-trimethoxyphenyl)propyl right bracket -5-aminotropolone using various oxidizing reagents.
Synthesis and biological evaluation of furanoallocolchicinoids
Voitovich, Yuliya V.,Shegravina, Ekaterina S.,Sitnikov, Nikolay S.,Faerman, Vladimir I.,Fokin, Valery V.,Schmalz, Hans-Gunther,Combes, Sebastien,Allegro, Diane,Barbier, Pascal,Beletskaya, Irina P.,Svirshchevskaya, Elena V.,Fedorov, Alexey Yu.
, p. 692 - 704 (2015)
A series of conformationally flexible furan-derived allocolchicinoids was prepared from commercially available colchicine in good to excellent yields using a three-step reaction sequence. Cytotoxicity studies indicated the potent activity of two compounds against human epithelial and lymphoid cell lines (AsPC-1, HEK293, and Jurkat) as well as against Wnt-1 related murine epithelial cell line W1308. The results of in vitro experiments demonstrated that the major effect of these compounds was the induction of cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding. In vivo testing of the most potent furanoallocolchicinoid 10c using C57BL/6 mice inoculated with Wnt-1 tumor cells indicated significant inhibition of the tumor growth.
Synthesis of new sulfur-containing derivatives of furanoallocolchicinoids
Gracheva, Yu. A.,Schmalz,Svirshchevskaya,Fedorov, A. Yu.
, p. 1137 - 1142 (2016)
Reaction of hydroxyl-containing heterocyclic colchicinoids with S-nucleophiles led to the formation of furanoallocolchicinoid sulfides in a high yield.
Synthesis and antiproliferative screening of novel analogs of regioselectively demethylated colchicine and thiocolchicine
Czerwonka, Dominika,Huczyński, Adam,Katrusiak, Andrzej,Maj, Ewa,Sobczak, Szymon,Wietrzyk, Joanna
supporting information, (2020/03/17)
Colchicine, a pseudoalkaloid isolated from Colchicum autumnale, has been identified as a potent anticancer agent because of its strong antimitotic activity. It was shown that colchicine modifications by regioselective demethylation affected its biological properties. For demethylated colchicine analogs, 10-demethylcolchicine (colchiceine, 1) and 1-demethylthiocolchicine (3), a series of 12 colchicine derivatives including 5 novel esters (2b-c and 4b-d) and 4 carbonates (2e-f and 4e- f) were synthesized. The antiproliferative activity assay, together with in silico evaluation of physicochemical properties, confirmed attractive biological profiles for all obtained compounds. The substitutions of H-donor and H-acceptor sites at C1 in thiocolchicine position provide an efficient control of the hydration affinity and solubility, as demonstrated for anhydrate 3, hemihydrate 4e and monohydrate 4a.
