1990-46-1

Upstream product

• 64-86-8 colchicine 
• 136570-06-4 10-(trifluoroacetyl)colchiceinamide 
• 3482-37-9 trimethylcolchicinic acid 
• 108-24-7 acetic anhydride 
• 7647-01-0 hydrogenchloride 
• 3123-89-5 N-[(7S)-1,2,3-trimethoxy-9-oxo-10-amino-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide 
• 2103-57-3 2,3,4-trimethoxybenzaldehyde 

Downstream Products

• 64-86-8 colchicine 
• 518-12-7 (7S)-isocolchicine 
• 75491-24-6 10-ethoxy-10-demethoxycolchicine 
• 75488-69-6 Ethyl isocolchicinate 
• 6714-14-3 allocolchicinic acid 
• 3482-37-9 trimethylcolchicinic acid 
• 6877-18-5 (S)-7-amino-1,2,3,10-tetrahydroxy-6,7-dihydro-5H-benzo[a]heptalen-9-one 
• 38838-27-6 (aR,5S)-N-(3-hydroxy-2-iodo-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-5-yl)-acetamide 
• 7622-04-0 N-((7S,9Ξ,10Ξ)-9,10-dihydroxy-1,2,3-trimethoxy-5,6,7,8,9,10,11,12-octahydro-benzo[a]heptalen-7-yl)-acetamide 
• 14686-56-7 O-benzoyl-O-demethylcolchicine 
• 2826-80-4 N-methyl colchiceinamide 
• 115102-08-4 N-((S)-1,2,3-trimethoxy-9-methylamino-10-oxo-5,6,7,10-tetrahydro-benzo[a]heptalen-7-yl)-acetamide 
• 7404-91-3 N-acetylisodemecolcine 
• 7336-40-5 N-acetyldemecolcine 

Relevant academic research and scientific papers

Fluorinated colchicinoids: Antitubulin and cytotoxic properties

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.

Synthesis of Colchicine C-10-Amino-Acid Derivatives

Colchicine derivatives modified on C-10 by natural and synthetic amino acids were synthesized.

Colchiceine complexes with lithium, sodium and potassium salts-spectroscopic studies

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.

Phospholipidic Colchicinoids as Promising Prodrugs Incorporated into Enzyme-Responsive Liposomes: Chemical, Biophysical, and Enzymological Aspects

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

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.

A convenient entry to new C-7-modified colchicinoids through azide alkyne [3+2] cycloaddition: Application of ring-contractive rearrangements

Reliable procedures for the preparation of azides derived from colchicine (1), allocolchicine (3) and N-acetylcolchinol (4a) were developed. These azides were then employed in Cu-catalyzed Huisgen-Sharpless [3+2] cycloaddition ("click") reactions with alkynes under microwave irradiation. The method developed opens a convenient and efficient access to libraries of new C-7-modified colchicinoids (triazole derivatives). In addition, a plausible mechanistic rationale for the colchicine-allocolchicine rearrangement is suggested. The Japan Institute of Heterocyclic Chemistry.

Synthesis and cytostatic properties of polyfunctionalized furanoallocolchicinoids

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).

Syntheses of colchicine and isocolchicine labelled with carbon-11 or carbon-13

The syntheses of isotopically labelled (-)-10-[11C/13C]-colchicine and (-)-9-[11C/13C]-isocolchicine have been achieved from the reaction of (-)desmethylcolchicine with [11C/13C]-iodomethane. The radiolabelled compounds, (-)-10-[11C]-colchicine (11C-n-colchicine) and (-)-9-[11C]-isocolchicine (11C-i-colchicine), were isolated by reversed phase HPLC. The total synthesis time was approximately 60 minutes for both radiolabelled compounds with an average specific activity of 240 mCi/μmol calculated to EOB. Utilizing a similar synthetic strategy, we also report the synthesis of milligram quantities of the carbon-13 enriched compounds and the magnetic resonance signal assignment for (-)-9-[13C] isocolchicine.

1-ACETAMIDO-3-(3,4,5-TRIMETHOXYPHENYL)PROPYL.

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.

Surface modified silica nanoparticles for synchronous magnetic resonance imaging and drug delivery applications

This study reports a simple and versatile method of tailoring surface modified silica nanoparticles (SMS NPs) via co-condensation technique. The particles were loaded with gadolinium oxide and an anticancer drug, colchicine, utilizing the aqueous core of the reverse micelle as "nano" host reactors. The surface of the silica NPs was modified with 3-aminopropyltriethoxysilane. Surface modification entails higher content of the drug and allows it to get released in a sustained manner. The particles exhibit spherical morphology with an average diameter of 60 nm as measured by TEM. Gadolinium oxide is paramagnetic in nature as observed from the NMR line broadening effect on proton spectrum of the surrounding water. Preliminary in vitro experiments on MCF-7 reveal good potential of these SMS NPs for cancer therapy. It is expected that these highly versatile multifunctional silica NPs could potentially be employed for simultaneous non-invasive imaging and therapeutic purposes.