Bio-inspired synthesis and biological evaluation of a colchicine-related compound library

Nicolaou, K. C.; Valiulin, Roman A.; Pokorski, Jonathan K.; Chang, Vicki; Chen, Jason S.

doi:10.1016/j.bmcl.2012.04.007

Cited by 34 publications

(16 citation statements)

References 49 publications

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“…Some derivatives of 1, such as thiocolchicoside (Neoflax™, Muscoril™) show improved therapeutic properties and clinical significance as anti-inflammatory, analgesic and anticancer drug [16,17]. Though medicinal use of 1 is limited many attempts have been made to discover more effective and less toxic analogues of 1 by modifying the substituents of its basic structure.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, antiproliferative and antibacterial evaluation of C-ring modified colchicine analogues

Huczyński¹,

Rutkowski²,

Popiel³

et al. 2015

European Journal of Medicinal Chemistry

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Section: Introductionmentioning

confidence: 99%

Synthesis, antiproliferative and antibacterial evaluation of C-ring modified colchicine analogues

Huczyński¹,

Rutkowski²,

Popiel³

et al. 2015

European Journal of Medicinal Chemistry

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“…For this reason, new derivatives obtained through chemical modifications guided by structure-activity relations are intensively investigated. This research is aimed at reducing the colchicine toxicity and preserving the antimitotic and anticancer properties [12][13][14][15][16][17][18][19][20][21][22][23][24]. As it turns out, tubulin interacts with trimethoxyphenyl ring A and tropolone ring C, making the methoxy groups at C1, C2 and C10, as well as the C9-keto group, crucial for colchicine's antimitotic activity [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antiproliferative Screening Of Novel Analogs of Regioselectively Demethylated Colchicine and Thiocolchicine

et al. 2020

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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.

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“…Ring B appears to be responsible for the irreversible nature of colchicine binding to tubulin, although it may also contribute to its toxic effects [ 11 , 17 ]. Therefore, currently much interest has focused on structural modification of 1 in the hope of improving its anticancer activity [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives

Majcher

Klejborowska

Moshari

et al. 2018

Cells

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Microtubules are tubulin polymer structures, which are indispensable for cell growth and division. Its constituent protein β-tubulin has been a common drug target for various diseases including cancer. Colchicine has been used to treat gout, but it has also been an investigational anticancer agent with a known antimitotic effect on cells. However, the use of colchicine as well as many of its derivatives in long-term treatment is hampered by their high toxicity. To create more potent anticancer agents, three novel double-modified colchicine derivatives have been obtained by structural modifications in C-4 and C-10 positions. The binding affinities of these derivatives of colchicine with respect to eight different isotypes of human β-tubulin have been calculated using docking methods. In vitro cytotoxicity has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo and LoVo/DX). Computer simulations predicted the binding modes of these compounds and hence the key residues involved in the interactions between tubulin and the colchicine derivatives. Two of the obtained derivatives, 4-bromothiocolchicine and 4-iodothiocolchicine, were shown to be active against three of the investigated cancer cell lines (A549, MCF-7, LoVo) with potency at nanomolar concentrations and a higher relative affinity to tumor cells over normal cells.

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Bio-inspired synthesis and biological evaluation of a colchicine-related compound library

Cited by 34 publications

References 49 publications

Synthesis, antiproliferative and antibacterial evaluation of C-ring modified colchicine analogues

Synthesis, antiproliferative and antibacterial evaluation of C-ring modified colchicine analogues

Synthesis and Antiproliferative Screening Of Novel Analogs of Regioselectively Demethylated Colchicine and Thiocolchicine

Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives

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