477-27-0Relevant articles and documents
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.
Phospholipidic Colchicinoids as Promising Prodrugs Incorporated into Enzyme-Responsive Liposomes: Chemical, Biophysical, and Enzymological Aspects
Shchegravina, Ekaterina S.,Tretiakova, Daria S.,Alekseeva, Anna S.,Galimzyanov, Timur R.,Utkin, Yuri N.,Ermakov, Yuri A.,Svirshchevskaya, Elena V.,Negrebetsky, Vadim V.,Karpechenko, Natalia Yu.,Chernikov, Valery P.,Onishchenko, Natalia R.,Vodovozova, Elena L.,Fedorov, Alexey Yu.,Boldyrev, Ivan A.
, p. 1098 - 1113 (2019/03/26)
Enzyme-responsive liposomes release their cargo in response to pathologically increased levels of enzymes at the target site. We report herein an assembly of phospholipase A2-responsive liposomes based on colchicinoid lipid prodrugs incorporated into lipid bilayer of the nanosized vesicles. The liposomes were constructed to addresses two important issues: (i) the lipid prodrugs were designed to fit the structure of the enzyme binding site; and (ii) the concept of lateral pressure profile was used to design lipid prodrugs that introduce almost no distortions into the lipid bilayer packing, thus ensuring that corresponding liposomes are stable. The colchicinoid agents exhibit antiproliferative activity in subnanomolar range of concentrations.
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 (2019/03/26)
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.
Gold-catalyzed cyclization in the synthesis of antimitotic 2,3-dihydrobenzo[b]oxepine derivatives of colchicine
Bukhvalova, S. Yu.,Maleev,Gracheva, Yu. A.,Voitovich, Yu. V.,Ignatov,Svirshchevskaya,Fedorov, A. Yu.
, p. 2205 - 2215 (2020/02/15)
New allocolchicine derivatives bearing 2,3-dihydrobenzo[b]oxepine moiety were synthesized via gold-catalyzed cyclization as a key synthetic step. The obtained 2,3-dihydrobenzo[b]oxepine-containing allocolchicinoids possess cytotoxic activity against HEK293, PANC-1, COL0357, HeLa, and Colon26 cancer cell lines at low micromolar range of concentrations.
Enantioselective total synthesis of (-)-colchicine, (+)-demecolcinone and metacolchicine: Determination of the absolute configurations of the latter two alkaloids
Chen, Bo,Liu, Xin,Hu, Ya-Jian,Zhang, Dong-Mei,Deng, Lijuan,Lu, Jieyu,Min, Long,Ye, Wen-Cai,Li, Chuang-Chuang
, p. 4961 - 4966 (2017/07/10)
Here, we describe a concise, enantioselective, and scalable synthesis of (-)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC50 = ～3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.
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 (2016/12/06)
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).
Synthesis of new sulfur-containing derivatives of furanoallocolchicinoids
Gracheva, Yu. A.,Schmalz,Svirshchevskaya,Fedorov, A. Yu.
, p. 1137 - 1142 (2016/10/04)
Reaction of hydroxyl-containing heterocyclic colchicinoids with S-nucleophiles led to the formation of furanoallocolchicinoid sulfides in a high yield.
Colchiceine complexes with lithium, sodium and potassium salts-spectroscopic studies
Kurek, Joanna,Barczynski, Piotr
, p. 297 - 308 (2017/01/21)
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.
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.
supporting information, p. 692 - 704 (2015/01/30)
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 Colchicine C-10-Amino-Acid Derivatives
Garazd, Ya. L.,Garazd,Kartsev
, p. 1138 - 1141 (2016/02/18)
Colchicine derivatives modified on C-10 by natural and synthetic amino acids were synthesized.
