2826-80-4Relevant articles and documents
Synthesis and antiproliferative screening of novel doubly modified colchicines containing urea, thiourea and guanidine moieties
Huczyński, Adam,Krzywik, Julia,Maj, Ewa,Mozga, Witold,Nasulewicz-Goldeman, Anna,Wietrzyk, Joanna
, (2021)
A new series of 10-demethoxy-10-methylaminocolchicines bearing urea, thiourea or a guanidine moieties at position C7 has been designed, synthesized and evaluated for in vitro anticancer activity against different cancer cell lines (A549, MCF-7, LoVo, LoVo/DX). The majority of the new derivatives were active in the nanomolar range and were characterized by lower IC50 values than cisplatin or doxorubicin. Two ureas (4 and 8) and thioureas (19 and 25) were found to be good antiproliferative agents (low IC50 values and high SI) and could prove to be promising candidates for further research in the field of anticancer drugs based on the colchicine skeleton.
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 (1999)
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, antiproliferative activity and molecular docking studies of novel doubly modified colchicine amides and sulfonamides as anticancer agents
Aminpour, Maral,Huczyński, Adam,Janczak, Jan,Krzywik, Julia,Maj, Ewa,Mozga, Witold,Tuszyński, Jack A.,Wietrzyk, Joanna
, (2020)
Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.
An insight into the anticancer potential of carbamates and thiocarbamates of 10-demethoxy-10-methylaminocolchicine
Krzywik, Julia,Aminpour, Maral,Janczak, Jan,Maj, Ewa,Moshari, Mahshad,Mozga, Witold,Wietrzyk, Joanna,Tuszyński, Jack A.,Huczyński, Adam
, (2021/02/26)
Colchicine shows very high antimitotic activity, therefore, it is used as a lead compound for generation of new anticancer agents. In the hope of developing novel, useful drugs with more favourable pharmacological profiles, a series of doubly modified colchicine derivatives has been designed, synthesized and characterized. These novel carbamate or thiocarbamate derivatives of 10-demethoxy-10-methylaminocolchicine have been tested for their antiproliferative activity against four human cancer cell lines. Additionally, their mode of action has been evaluated as colchicine binding site inhibitors, using molecular docking studies. Most of the tested compounds showed greater cytotoxicity (IC50 in a low nanomolar range) and were characterized by a higher selectivity index than standard chemotherapeutics such as cisplatin and doxorubicin as well as unmodified colchicine. Their pharmacological use in cancer therapy could possibly be accomplished with lower dosages and result in less acute toxicity problems than in the case of colchicine. In addition, we present a QSAR model for predicting the antiproliferative activity of doubly modified derivatives for two tumour cell lines.
New series of double-modified colchicine derivatives: Synthesis, cytotoxic effect and molecular docking
Aminpour, Maral,Huczyn?ski, Adam,Krzywik, Julia,Maj, Ewa,Mozga, Witold,Tuszyn?ski, Jack A.,Wietrzyk, Joanna
supporting information, (2020/08/28)
Colchicine is a well-known anticancer compound showing antimitotic effect on cells. Its high cytotoxic activity against different cancer cell lines has been demonstrated many times. In this paper we report the syntheses and spectroscopic analyses of novel colchicine derivatives obtained by structural modifications at C7 (carbon-nitrogen single bond) and C10 (methylamino group) positions. All the obtained compounds have been tested in vitro to determine their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX, and BALB/3T3 cell lines. The majority of obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin and cisplatin against the tested cancerous cell lines. Additionally, most of the presented derivatives were able to overcome the resistance of LoVo/DX cells. Additionally, their mode of binding to β-tubulin was evaluated in silico. Molecular docking studies showed that apart from the initial amides 1 and 2, compound 14, which had the best antiproliferative activity (IC50 = 0.1–1.6 nM), stood out also in terms of its predicted binding energy and probably binds best into the active site of βI-tubulin isotype.
Synthesis and antitumour activity of novel colchicine C-10 derivatives
Shen, Li Hong,Zhang, Le,Wang, Hai Xian,Wang, Xin,Zhang, Gai Jiao
, p. 7475 - 7476 (2015/04/22)
A series of new colchicine C-10 derivatives (2a-i, 3a-h) were synthesized by replacement of the 10-methoxy with NR2 and SCH3 in order to determine their cytotoxic activity. The compounds were synthesized in good yield and the structures of all newly synthesized compounds were established on the basis of their IR, 1H NMR and elemental analysis. The synthesized compounds were tested in vitro antitumor activity against four human cancer cell lines by MTT assay. It was found that many of the derivatives displayed significant activity, particularly, compound 2a and 2b showed more potent cytotoxic activities than colchicine.
Antitumor agents. Part 186: Synthesis and biological evaluation of demethylcolchiceinamide analogues as cytotoxic DNA topoisomerase II inhibitors
Guan, Jian,Zhu, Xiao-Kang,Tachibana, Yoko,Bastow, Kenneth F.,Brossi, Arnold,Hamel, Ernest,Lee, Kuo-Hsiung
, p. 2127 - 2131 (2007/10/03)
Demethylation of colchiceinamide (2) and its analogues (3-10) afforded a novel class of mammalian DNA topoisomerase II inhibitors (2a-10a) without displaying tubulin inhibitory activity. All target compounds inhibited the catalytic activity of topoisomera
