3482-37-9Relevant academic research and scientific papers
Discovery of structurally simplified analogs of colchicine as an immunosuppressant
Chang, Dong-Jo,Kim, Wan-Joo
, p. 3121 - 3125 (2014/06/24)
We have discovered a new class of colchicine-derived therapeutic agents for immune diseases including rejection of organ-transplantation and autoimmune disease. Compound 2, which had been developed to overcome poor pharmacokinetic properties of compound 1, a first-generation colchicine analog, turned out to show toxicity such as intestinal toxicity and loss of weight during in vivo tests. The deletion of 7-carboxamide group and middle ring-truncation in colchicine allowed us to have structurally simplified analogs with strong immunosuppressive activity. Herein, we report non-alkaloid tricyclic compound 7 and 12 as immunosuppressants which exhibited a strong immunosuppressive in vivo efficacy on the T-dependent antibody response, the Zymosan A-induced arthritis model and the Carrageenan-induced edema model. Compound 7 and 12 revealed less toxicity than the previous lead compound 2, and their minimum lethal doses (MLD) were proved to exceed 100 mg/kg.
99mTc-labeling of colchicine using [99mTc(CO) 3(H2O)3]+ and [ 99mTc≡N]2+ core for the preparation of potential tumor-targeting agents
Korde, Aruna,Satpati, Drishty,Mathur, Anupam,Mallia, Madhava,Banerjee, Sharmila,Kothari, Kanchan,Sarma,Choudhari, Pradeep,Venkatesh, Meera
, p. 793 - 799 (2007/10/03)
Multidrug resistance (MDR) mediated by over-expression of P-glycoprotein (Pgp) is one of the major causes of failure of chemotherapy in cancer treatment. Colchicine, a naturally occurring alkaloid, is a Pgp substrate and acts as an antimitotic agent by binding to microtubules. Hence, Colchicine and its analogues radiolabeled with 99mTc may have potential for visualization of MDR in tumors. Here we report 99mTc-labeling of colchicine derivatives using [99mTc(CO)3(H 2O)3]+ and [99mTc≡N] 2+ cores. Trimethylcolchicinic acid synthesized from colchicine was used as the precursor to prepare iminodiacetic acid and dithiocarbamate derivatives which were then radiolabeled with [99mTc(CO) 3(H2O)3]+ and [ 99mTc≡N]2+ cores, respectively. Radiolabeling yield for both the complexes was >98% as observed by HPLC and TLC patterns. In vitro studies in tumor cell lines showed significant uptake for 99mTc-carbonyl as well as for 99mTc-nitrido colchicine complexes. Biodistribution studies in Swiss mice bearing fibrosarcoma tumor showed 4.1 ± 1.2% ID/g of uptake at 30 min pi for 99mTc(CO) 3-complex as against 0.42 ± 0.24% ID/g for the 99mTcN-complex. 99mTc(CO)3-colchicine complex exhibited better pharmacokinetics with lower liver accumulation as compared to the 99mTcN-complex. Thus, colchicine radiolabeled with [ 99mTc(CO)3(H2O)3]+ core is more promising with respect to in vivo distribution characteristics in tumor model.
Synthesis and evaluation of 90Y-DOTA-colchicine conjugate in murine fibrosarcoma model
Satpati, Drishty,Korde, Aruna,Pandey, Usha,Dhami, Prem,Banerjee, Sharmila,Venkatesh, Meera
, p. 951 - 958 (2008/02/04)
Colchicine is a cytotoxic bioactive alkaloid that exhibits its action by microtubular binding. With an aim to develop a tumor targeted radio-therapeutic agent, colchicine has been functionalized to trimethylcolchicinic acid and conjugated to the isothiocyanato derivative of DOTA (1,4,7,10-tetraaza cyclododecane tetracetic acid). DOTA coupled colchicine was radiolabeled with 90Y, one of the most commonly used therapeutic radioisotope. Complexation of 200 μg of the conjugate with 90Y was carried out at pH 4.5 with an incubation time of 45 min at 70°C. Complexation yield of 90Y-DOTA-NCS-colchicine was confirmed to be >98% using C-18 reverse phase HPLC system. 90Y-colchicine complex could be differentiated from 90Y-p-NCS-benzyl-DOTA on the basis of difference in their retention times 8 and 4 min, respectively in a standardized HPLC system. Biodistribution studies in Swiss mice fibrosarcoma tumor model showed an uptake of ～0.8% ID/g tumor at 3 h.p.i. that was retained till 24 h.p.i. 90Y-DOTA-NCS-colchicine complex showed excellent pharmacokinetics with major portion of the radioactivity being excreted out within 3 h.p.i. and no accumulation of radioactivity in vital organs. Copyright
100. From Colchicine and Some of Its Derivatives to 1,2,3,9,10-Pentamethoxybenzoheptalenes
Kouroupis, Pavlos,Hansen, Hans-Jurgen
, p. 1247 - 1277 (2007/10/02)
A two-step synthesis of 4-methylcolchicine (13), starting from colchicine (2), has been developd (Scheme 5).In three steps, 4-ethylcolchicine (28) is also accessible from 2 (Scheme 8).Colchicine (2) and its derivatives 13 and 28 have been transformed into the benzoheptalene derivatives 9,18, and 34, respectively, by Hofmann degradation of the corresponding deacetylcolchiceine 3, 19, and 29, respectively, followed by methylation of the two O-functions first with diazomethane and then with trimethoxonium tetrafluoroborate (Scheme 2 and 6).The thus formed tropylium salts gave, on deprotonation with Me3N in CHCl3, the expected pentamethoxybenzoheptalenes 9, 18, and 34, respectively.X-Ray crystal-structure analysis of 9 (Fig.3) and 18 (Fig.7), determination of the vicinal coupling constants of the H-atoms at the heptalene skeleton as well as the measurement of the racemization rate of the heptalene skeleton.The absolute configuration of the resolved heptalenes was deduced from their long-wavelength CD maxima around 350 nm.The heptalenes with a negative maximum in this range possess (7aP)-configuration.
Syntheses of colchicine and isocolchicine labelled with carbon-11 or carbon-13
Kothari,Finn,Larson
, p. 521 - 528 (2007/10/02)
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.
STRUCTURES OF TETRA-O-DEMETHYLCOLCHICINE, -ISOCOLCHICINE, AND 10-O-DEMETHYLCOLCHICINE DERIVATIVES
Kashiwada, Yoshiki,Sun, Li,Tatematsu, Hiroshi,Bastow, Kenneth F.,Lee, Kuo-Hsiung
, p. 2531 - 2540 (2007/10/02)
During the exhaustive demethylation of both colchicine and isocolchicine analogs, tetra-O-demethyl derivatives with identical structures were produced.Spectral examination (1H-13C long-range COSY nuclear magnetic resonanse) of these analogs (5-8) indicated that isocolchicine-type tautomerism is predominant in tetra-O-demethylcolchicine derivatives.Similarly, structures of 10-O-demethylcolchicine derivatives were revised to be an isocolchicine-type shown by formulae (9) and (10).
Semisyntheses, X-Ray Crystal Structures and Tubulin-Binding Properties of 7-Oxodeacetamidocolchicine and 7-Oxodeacetamidoisocolchicine
Banwell, Martin G.,Peters, Steven C.,Greenwood, Richard J.,Mackay, Maureen F.,Hamel, Ernest,Lin, Chii M.
, p. 1577 - 1588 (2007/10/02)
Commercially available (-)-colchicine (1) has been converted, via deacetylcolchiceine (4), into a mixture of 7-oxodeacetamidocolchicine (2) and 7-oxodeacetamidoisocolchicine (3).The X-ray structures and tubulin-binding properties of these title ketones are described.
