Evaluation of the cytotoxic, apoptosis inducing activity and molecular docking of spiroquinazolinone benzamide derivatives in MCF-7 breast cancer cells

Mahdavi, Majid; Lavi, Malihe Mohseni; Yekta, Reza; Moosavi, Mohammad Amin; Nobarani, Mahnaz; Balalaei, Saeed; Arami, Sanam; Rashidi, Mohammad

doi:10.1016/j.cbi.2016.10.004

Cited by 33 publications

(12 citation statements)

References 43 publications

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“…ROS is a medium factor of apoptosis signal channel. A large number of researches have shown that high level ROS could lead to DNA destruction, MMP dysfunction, and cell apoptosis [37,42]. In our work, after treatment with appointed concentration of SSCC in MCF-7 and BT-20 cells, the generation of ROS significantly increased and MMP distinctly decreased in a time-dependent manner.…”

Section: Discussionmentioning

confidence: 52%

“…Moreover, in this study, NAC as a free radical scavenger blocked the toxic effects of SSCC on MCF-7 and BT-20 cells in vitro. Similarly, according to the report of Mahdaviet al [37], 50 μM spiroquinazolinone benzamide led to the apoptosis of MCF-7 cells and the apoptosis rate reached to 28% after treatment for 72 h. Meanwhile, When BT-20 cells were treated with N-Hydroxyphthalimide at 10 μM, the total percentage of apoptotic cells increased about 8.8-fold compared with control [38]. In contrast, SSCC-induced breast cancer cells including MCF-7 and BT-20 cells have a higher apoptosis rate than other chemical compounds.…”

Section: Discussionmentioning

confidence: 92%

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Seleno-short-chain chitosan induces apoptosis in human breast cancer cells through mitochondrial apoptosis pathway in vitro

Zhao

et al. 2018

Cell Cycle

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Seleno-short-chain chitosan (SSCC) was a synthesized chitosan derivative with the molecular weight of 4826.986 Da. The study is aimed to investigate cytotoxicity of SSCC on human breast cancer MCF-7 and BT-20 cells and explore apoptosis-related mechanism in vitro. The MTT (3- [4,5-Dimethylthiazol-2-yl]-2, 5-diphenylterazolium bromide) assay showed that SSCC exhibited significantly cytotoxic effects on MCF-7 and BT-20 cells in a dose- and time-dependent manner, and the effective inhibitory concentration was 100 μg/ml and 200 μg/ml, respectively. Apoptosis assay of these two kinds of cells was determined by Hoechst 33,342/PI and Annexin V-FITC/PI double staining. The cell cycle assay showed that SSCC triggered S and G2/M phase cell cycle arrest in MCF-7 cells and S phase cell cycle arrest in BT-20 cells in a time-dependent manner. Further studies demonstrated that SSCC led to the generation of reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential (MMP) in these two kinds of cells. N- acetyl-L cysteine (NAC), as a radical scavenger, significantly inhibited the generation of ROS and decreased the apoptosis of MCF-7 and BT-20 cells. Moreover, the expression of mitochondrial apoptosis-related proteins was detected by western blot assay. SSCC up-regulated the expression of Bax, down-regulated the expression of Bcl-2, subsequently increased the release of cytochrome c from mitochondria to cytoplasm, and activated the cleavage of caspase-9 and -3, which finally induced apoptosis in MCF-7 and BT-20 cells in vitro. Consequently, these data indicated that SSCC could induce apoptosis of MCF-7and BT-20 cells in vitro by mitochondrial pathway.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 92%

Seleno-short-chain chitosan induces apoptosis in human breast cancer cells through mitochondrial apoptosis pathway in vitro

Zhao

et al. 2018

Cell Cycle

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“…These derivatives are similar to chalcone derivatives in our previous investigations. In fact, recently, a lot of benzamide and picolinamide derivatives were investigated as anticancer agents 14 , DNA minor groove binders 15 , 11 b-hydroxysteroid dehydrogenase inhibitos 16 or metabotropic glutamate receptor 5 antagonists 17 , but few investigations on the bioactivity of them in inhibiting AChE or BChE were reported 18 . In order to study the possible inhibition profile and mechanism of new synthesised compounds, enzyme kinetic experiments and molecular docking studies were performed.…”

Section: Introductionmentioning

confidence: 99%

Structure–activity relationship investigation of benzamide and picolinamide derivatives containing dimethylamine side chain as acetylcholinesterase inhibitors

Gao

Linbo

Liu

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of benzamide and picolinamide derivatives containing dimethylamine side chain (4a–4c and 7a–7i) were synthesised and evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity in vitro. Structure–activity relationship investigation revealed that the substituted position of dimethylamine side chain markedly influenced the inhibitory activity and selectivity against AChE and BChE. In addition, it seemed that the bioactivity of picolinamide amide derivatives was stronger than that of benzamide derivatives. Among them, compound 7a revealed the most potent AChE inhibitory activity (IC50: 2.49 ± 0.19 μM) and the highest selectivity against AChE over BChE (Ratio: 99.40). Enzyme kinetic study indicated that compound 7a show a mixed-type inhibition against AChE. The molecular docking study revealed that this compound can bind with both the catalytic site and the peripheral site of AChE.

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“…Human leukemia cells K562 were grown in RPMI 1640 medium supplemented with 10% FBS, 1% streptomycin and 1% penicillin and placed in an incubator under 5% CO 2 in air at 37°C …”

Section: Methodsmentioning

confidence: 99%

“…K562 cells were seeded into 24‐well plates (5 × 10 5 cells/well). Subsequently, seeded cells were treated with the DBP‐g compound at the respective IC 50 concentration (55 μM) for 24, 48 or 72 h. Cells were collected by centrifugation and washed with phosphate‐buffered saline (PBS), then AO/EtBr solution (1:1, v/v) was added to 10 μl of the cells and, finally, morphologically changed cells were assessed using a fluorescence microscopy …”

Section: Methodsmentioning

confidence: 99%

DNA‐binding activity and cytotoxic and cell‐cycle arrest properties of some new coumarin derivatives: a multispectral and computational investigation

et al. 2019

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Coumarins are the most important class of natural compounds found widely in various plants. Many coumarin derivatives with different biological and pharmacological activities have been synthesized. In this study, the antiapoptotic and cytotoxic effects and DNA-binding properties of some synthetic coumarin derivatives (4b, 4d, 4f, 4 g (DBP-g), 4 h and 4j) against K562 cell lines were investigated using different techniques. MTT assay indicated that the DBP-g compound was more active than other derivatives, with a IC 50 value of 55 μM, and therefore this compound was chosen for further investigation. Apoptosis induction was assessed using acridine orange/ethidium bromide double-staining and cell-cycle analysis. In addition, in vitro DNA-binding studies were carried out using ultraviolet-visible light absorption and fluorescence spectroscopy, as well as viscosity measurement and molecular modelling studies. In vitro results indicated that DBP-g interacted with DNA through a groovebinding mode with a binding constant (K b ) of 1.17 × 10 4 M −1 . In agreement with other experimental data, molecular docking studies showed that DBP-g is a minor groove binder. Overall, it can be concluded that DBP-g could be used as an effective and novel chemotherapeutic agent.

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Evaluation of the cytotoxic, apoptosis inducing activity and molecular docking of spiroquinazolinone benzamide derivatives in MCF-7 breast cancer cells

Cited by 33 publications

References 43 publications

Seleno-short-chain chitosan induces apoptosis in human breast cancer cells through mitochondrial apoptosis pathway in vitro

Seleno-short-chain chitosan induces apoptosis in human breast cancer cells through mitochondrial apoptosis pathway in vitro

Structure–activity relationship investigation of benzamide and picolinamide derivatives containing dimethylamine side chain as acetylcholinesterase inhibitors

DNA‐binding activity and cytotoxic and cell‐cycle arrest properties of some new coumarin derivatives: a multispectral and computational investigation

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