Synthesis, biological evaluation and molecular docking studies of aminochalcone derivatives as potential anticancer agents by targeting tubulin colchicine binding site

Wang, Guangcheng; Peng, Zhiyuan; Zhang, Jiebing; Qiu, Jie; Xie, Zhenzhen; Gong, Zipeng

doi:10.1016/j.bioorg.2018.03.028

Cited by 48 publications

(31 citation statements)

References 37 publications

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“…Chemistry The synthesis of chalcone derivatives containing indole and naphthalene moieties (2-19) is shown in Chart Table 1, introduction methyl group at the N-1 position result in slight increase of anticancer activity (7). However, the replacement of H with substitute benzyl group (6,(12)(13)(14)(15)(16)(17)(18)(19) or other bulk alkyl group (8)(9)(10)(11) at N-1 position of indole ring resulted in a remarkable increase of the biological activity.…”

Section: Resultsmentioning

confidence: 99%

“…Because of these observations and following our interest in design and synthesis of novel tubulin polymerization inhibitors, 17,18) herein we report for the first time the synthesis of a novel series of chalcone derivatives containing indole and naphthalene moieties.…”

Section: Introductionmentioning

confidence: 94%

“…1). On the other hand, several compounds containing naphthalene moiety have been reported as potent anticancer agents that inhibit tubulin polymerization [16][17][18] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

“…The in Vitro Anticancer Activities of Chalcone Derivatives Containing Indole and Naphthalene Moieties(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) …”

mentioning

confidence: 99%

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Synthesis, Anticancer Activity and Molecular Modeling Studies of Novel Chalcone Derivatives Containing Indole and Naphthalene Moieties as Tubulin Polymerization Inhibitors

Wang

Peng

2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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Eighteen novel chalcone derivatives containing indole and naphthalene moieties (2-19) were synthesized and characterized by 1 H-NMR, 13 C-NMR and high resolution (HR)-MS spectra. All compounds were evaluated for their in vitro cytotoxic potential against human hepatocellular carcinoma (HepG2), human colon carcinoma (HCT116) and human breast adenocarcinoma (MCF-7) cell lines. Among them, compound 2, 3, 4 and 7 showed potent activities against tested cancer cell lines. More significantly, compound 7 exhibited the most potent cytotoxic activity against HepG2, HCT116 and MCF-7 with IC 50 values of 0.65, 1.13 and 0.82 µM, respectively. Furthermore, flow cytometry analysis indicated that compound 7 arrested cancer cells in G2/M phase. The compound 7 also displayed significant inhibition of tubulin polymerization (IC 50 3.9 µM). Finally, molecular docking studies were performed to explore the possible interactions between compound 7 and tubulin binding pockets.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

“…1). On the other hand, several compounds containing naphthalene moiety have been reported as potent anticancer agents that inhibit tubulin polymerization [16][17][18] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

“…The in Vitro Anticancer Activities of Chalcone Derivatives Containing Indole and Naphthalene Moieties(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) …”

mentioning

confidence: 99%

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Synthesis, Anticancer Activity and Molecular Modeling Studies of Novel Chalcone Derivatives Containing Indole and Naphthalene Moieties as Tubulin Polymerization Inhibitors

Wang

Peng

2019

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…7-azindole derivatives have been found to be an important scaffold in the anticancer drug like Vemurafenib [8]. Chalcone derivatives have been an important class of compounds which is used as anticancer agents [9]. Hence conjugating the azaindole ring with chalcone could improve the binding affinity of compound which in turn the pharmacological activity increases.…”

Section: Introductionmentioning

confidence: 99%

Design of Chalcones of 7-Azaindole as Raf-B Inhibitors

Giles¹,

Saiprabha²,

Yeshna³

2019

JACS

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The present work deals with the design of 7-azaindole derivatives for its Raf-B inhibition. All the designed compounds follows Lipinski’s rule of five. In silico ADME predictions of all the designed compounds suggests that none of the compounds have problem with bioavailability. The compounds were designed on the binding affinity towards the Raf-B inhibition. It was observed that few of the designed compounds were found to have significant interaction with the active site of the receptor. The compounds possessing 3-hydroxyl-2-methyl as substitution in chalcone was found to possess maximum docking score than other designed compounds.

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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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Synthesis, biological evaluation and molecular docking studies of aminochalcone derivatives as potential anticancer agents by targeting tubulin colchicine binding site

Cited by 48 publications

References 37 publications

Synthesis, Anticancer Activity and Molecular Modeling Studies of Novel Chalcone Derivatives Containing Indole and Naphthalene Moieties as Tubulin Polymerization Inhibitors

Synthesis, Anticancer Activity and Molecular Modeling Studies of Novel Chalcone Derivatives Containing Indole and Naphthalene Moieties as Tubulin Polymerization Inhibitors

Design of Chalcones of 7-Azaindole as Raf-B Inhibitors

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

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