Antiproliferative Activity of Tubuloclustin and its Steroid Analogs

Zefirova, O. N.; Nurieva, E. V.; Glazkova, Iana S.; Zefirov, N. A.; Mamaeva, A. V.; Wobith, Birgit; Романенко, В. И.; Lesnaya, N. A.; Трещалина, Е. М.; Kuznetsov, Sergey A.

doi:10.1007/s11094-014-1113-8

Cited by 9 publications

(4 citation statements)

References 11 publications

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“…A number of colchicine–adamantane conjugates of type 204 − with ester linkers of varying length were synthesized using EEDQ ( N -ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) as a reagent (Scheme ). These compounds were shown to exhibit cytotoxic activity at low nanomolar concentrations.…”

Section: Hybrids Conjugates and Prodrugs Of Colchicinoids: Colchicino...mentioning

confidence: 99%

Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives

et al. 2020

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Colchicine, the main alkaloid of Colchicum autumnale, is one of the most famous natural molecules. Although colchicine belongs to the oldest drugs (in use since 1500 BC), its pharmacological potential as a lead structure is not yet fully exploited. This review is devoted to the synthesis and structure− activity relationships (SAR) of colchicine alkaloids and their analogues with modified A, B, and C rings, as well as hybrid compounds derived from colchicinoids including prodrugs, conjugates, and delivery systems. The systematization of a vast amount of information presented to date will create a paradigm for future studies of colchicinoids for neoplastic and various other diseases.

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Section: Hybrids Conjugates and Prodrugs Of Colchicinoids: Colchicino...mentioning

confidence: 99%

Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives

et al. 2020

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“…The majority of anticancer agents interacting with colchicine binding site (located in β-tubulin at the intradimeric interface of the heterodimer) under normal conditions are causing depolymerization of MTs only [7]. However, some ligands of colchicine domain can in addition stimulate the formation of atypical tubulin assemblies [8][9][10][11][12][13][14][15][16]. Many of these ligands represent colchicine (1a, Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Many of these ligands represent colchicine (1a, Fig. 1) derivatives, able to provide hydrophobic contacts with α-tubulin subunit [10][11][12][13][14]. Tubuloclustin (1b) is a typical example of such compound: it initiates MT depolymerization with the following formation of tubulin clusters [10,14].…”

Section: Introductionmentioning

confidence: 99%

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Novel colchicine conjugate with unusual effect on the microtubules of cancer cells

Zefirova

Nurieva

Wobith

et al. 2020

Pure and Applied Chemistry

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AbstractColchicine derivative bearing substituted bispidine moiety, namely N-{7-(3,7-Di-(tert-butoxycarbonyl)-1,5-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-yl)-oxy-7-oxoheptanoyl}-N-deacetylcolchicine, was synthesized and tested for its effect on the net of microtubules (MT) in lung cancer cells A549. The compound induced not only MT depolymerization but stimulated the formation of small tubulin aggregates and long tubulin fibrils localized mainly around nuclei. The assemblies were morphologically different from tubulin clusters induced by structurally related anticancer agent tubuloclustin. The biotests data demonstrate that the depolymerization takes place for both pure tubulin and tubulin in cellulo, while fibrils are formed only in the cells. The research data of structure–activity relationship for several similar colchicine derivatives synthesized in the work give evidence for the proposition that the initial conjugate may interact not only with tubulin and MT in the cells, but also with MT-associated proteins, involved in the process of tubulin polymerization. The ability to affect simultaneously MAP – tubulin interactions opens attractive prospects in the design of novel anticancer agents.

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Novel antimitotic agents related to tubuloclustin: synthesis and biological evaluation

et al. 2017

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Tubuloclustin [N-(7-adamant-2-yloxy-7-oxoheptanoyl)-N-deacetylcolchicine], a highly cytotoxic anti-tubulin compound is known for its ability to promote microtubule disassembly followed by the formation of tubulin clusters of unique morphology. Three series of antimitotic agents related to tubuloclustin were designed and synthesized in order to enhance the molecular diversity of "tubuloclustin-like" family of compounds. The series of compounds with modified adamantane moiety was highly potent in cytotoxic effect on human lung carcinoma A549 cells (EC50 = 6-400 nM) and was active in affecting the microtubule arrays and induction of strong tubulin clusterization. In two other sets of compounds, the colchicine moiety of tubuloclustin was replaced by podophyllotoxin or combretastatin A-4. All combretastatin A-4 derivatives displayed noticeable cytotoxic activity ([Formula: see text]) but their effect on microtubules depended on the position of the linker attachment. Podophyllotoxin derivatives were also toxic to A549 cells ([Formula: see text]) and caused both microtubule depolymerization and some tubulin clustering. The data obtained gave additional evidence that the whole panel of C7-colchicine, podophyllotoxin and combretastatin derivatives could manifest clustering effect, and the strength of this effect correlated with cytotoxic activity of the compounds.

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Antiproliferative Activity of Tubuloclustin and its Steroid Analogs

Cited by 9 publications

References 11 publications

Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives

Colchicine Alkaloids and Synthetic Analogues: Current Progress and Perspectives

Novel colchicine conjugate with unusual effect on the microtubules of cancer cells

Novel antimitotic agents related to tubuloclustin: synthesis and biological evaluation

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