Methylene versus carbonyl bridge in the structure of new tubulin polymerization inhibitors with tricyclic A-rings

Moise, Iuliana-Monica; Bîcu, Elena; Dubois, Joëlle; Farce, Amaury; Rigo, Benoı̂t; Ghinet, Alina

doi:10.1016/j.bmc.2016.09.063

Cited by 6 publications

(2 citation statements)

References 35 publications

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“…On the contrary, microtubules play a crucial role in mitosis and have been long considered as an important target for the development of novel anticancer drugs. By interfering with microtubule dynamics, inhibitors of tubulin arrest the cell into mitosis, leading to cell death through apoptosis as well as necrosis . Colchicine (Figure ) is an alkaloid isolated from Colchicum autumnale and Gloriosa superba and the first drug known to bind tubulin at a particular site called the colchicine domain .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of novel benzo[c]acridine‐diones as potential anticancer agents and tubulin polymerization inhibitors

Behbahani

Tabeshpour

Mirzaei

et al. 2019

Archiv der Pharmazie

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A new series of novel benzo[c]acridine-diones possessing pharmacophoric elements of antitubulins with central dihydropyridine bridge were designed and synthesized as potential anticancer agents and tubulin polymerization inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against eight cancer cell lines including MCF-7, A2780, HeLa, HepG2, DU145, A549, PC3, and LNCAP cancer cells and normal cells (HUVEC) through 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide (MTT) assay, wherein β-lapachone and combretastatin A-4 were used as positive controls. Some of our compounds (4c and 4g) showed significant cytotoxic activity on cancer cells with IC 50 values in the range of 5.23-24.32 μM. None of the synthesized compounds showed significant cytotoxicity on normal HUVEC cells. Among all investigated derivatives, compound 4g showed promising greater antiproliferative activity against all tested cancer cells with the highest sensitivity observed for the PC3 cell line. Results from the flow cytometry analysis of PC3 and MCF-7 cancer cells treated with 4g showed an induced cell-cycle arrest at G2/M, and therefore induced apoptosis which occurred at low concentration of test compound, whereas annexin V-FITC/propidium iodide staining assay in the aforementioned cancer cell lines treated with 4g showed that 4g can cause necrosis in PC3 and MCF-7 cancer cells at higher concentration. Compound 4g proved to be an inhibitor of tubulin polymerization in a mode similar to that of colchicine and in a dose-dependent manner. Molecular docking studies of 4g into the colchicine-binding site of tubulin exhibited a possible mode of interaction between this compound and tubulin.

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Section: Introductionmentioning

confidence: 99%

Synthesis and biological evaluation of novel benzo[c]acridine‐diones as potential anticancer agents and tubulin polymerization inhibitors

Behbahani

Tabeshpour

Mirzaei

et al. 2019

Archiv der Pharmazie

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“…Antimitotic drugs have been successfully used as chemotherapeutic agents in management of cancer via disruption of microtubule/tubulin dynamics . Microtubules are important cytoskeletal structures formed by polymerization of α and β tubulin heterodimers, which play a crucial role in the formation of mitotic spindle required for proper chromosomal separation during cell division.…”

Section: Introductionmentioning

confidence: 99%

New 3‐Substituted‐2‐(4‐hydroxyanilino)pyridine Derivatives: Synthesis, Antitumor Activity, and Tubulin Polymerization Inhibition

Elmeligie

Khalil

Ahmed

et al. 2017

Archiv der Pharmazie

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A series of new pyridine derivatives 4a-c, 5a-d, 6a-d, 7a-f, and 8a-f structurally related to ABT-751 were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were tested for their cytotoxic activity in vitro against the HCT-116 and HepG-2 cancer cell lines using the MTT assay. The results showed that compound 8d has higher cytotoxic activity than the reference antimitotic agent colchicine, against both tested cell lines, with IC = 0.52 and 1.40 μM, respectively. The three most active compounds, 5d, 8b, and 8d, were further screened in vitro for inhibition of tubulin and showed remarkable results in comparison to colchicine.

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Seven-Membered Rings

Meyer

Bissember

Hyland

et al. 2017

Progress in Heterocyclic Chemistry

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Methylene versus carbonyl bridge in the structure of new tubulin polymerization inhibitors with tricyclic A-rings

Cited by 6 publications

References 35 publications

Synthesis and biological evaluation of novel benzo[c]acridine‐diones as potential anticancer agents and tubulin polymerization inhibitors

Synthesis and biological evaluation of novel benzo[c]acridine‐diones as potential anticancer agents and tubulin polymerization inhibitors

New 3‐Substituted‐2‐(4‐hydroxyanilino)pyridine Derivatives: Synthesis, Antitumor Activity, and Tubulin Polymerization Inhibition

Seven-Membered Rings

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