scholarly journals Synthesis and Biological Evaluation of 2-Substituted Benzyl-/Phenylethylamino-4-amino-5-aroylthiazoles as Apoptosis-Inducing Anticancer Agents

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2177
Author(s):  
Paola Oliva ◽  
Valentina Onnis ◽  
Elisa Balboni ◽  
Ernest Hamel ◽  
Francisco Estévez-Sarmiento ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Thiazole Derivatives ◽  
Concentration Dependent Manner ◽  
Cyclin Dependent Kinases

Induction of apoptosis is a common chemotherapeutic mechanism to kill cancer cells The thiazole system has been reported over the past decades as a building block for the preparation of anticancer agents. A novel series of 2-arylalkylamino-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)-thiazole derivatives designed as dual inhibitors of tubulin and cyclin-dependent kinases (CDKs) were synthesized and evaluated for their antiproliferative activity in vitro against two cancer cell lines and, for selected highly active compounds, for interactions with tubulin and cyclin-dependent kinases and for cell cycle and apoptosis effects. Structure-activity relationships were elucidated for various substituents at the 2-position of the thiazole skeleton. Among the synthesized compounds, the most active analogues were found to be the p-chlorobenzylamino derivative 8e as well as the p-chloro and p-methoxyphenethylamino analogues 8f and 8k, respectively, which inhibited the growth of U-937 and SK-MEL-1 cancer cell lines with IC50 values ranging from 5.7 to 12.2 μM. On U-937 cells, the tested compounds 8f and 8k induced apoptosis in a time and concentration dependent manner. These two latter molecules did not affect tubulin polymerization (IC50 > 20 μM) nor CDK activity at a single concentration of 10 μM, suggesting alternative targets than tubulin and CDK for the compounds.

scholarly journals Design, Synthesis and Biological Evaluation of a New Series of 1-Aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea Derivatives as Antiproliferative Agents

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2108 ◽  
Author(s):  
Chuanming Zhang ◽  
Xiaoyu Tan ◽  
Jian Feng ◽  
Ning Ding ◽  
Yongpeng Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
A549 Cells ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Urea Derivatives ◽  
Antiproliferative Agents

To discover new antiproliferative agents with high efficacy and selectivity, a new series of 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea derivatives (7a–7t) were designed, synthesized and evaluated for their antiproliferative activity against A549, HCT-116 and PC-3 cancer cell lines in vitro. Most of the target compounds demonstrated significant antiproliferative effects on all the selective cancer cell lines. Among them, the target compound, 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-{4-{{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}thio}phenyl}urea (7i) was identified to be the most active one against three cell lines, which was more potent than the positive control with an IC50 value of 1.53 ± 0.46, 1.11 ± 0.34 and 1.98 ± 1.27 μM, respectively. Further cellular mechanism studies confirmed that compound 7i could induce the apoptosis of A549 cells in a concentration-dependent manner and elucidated compound 7i arrests cell cycle at G1 phase by flow cytometry analysis. Herein, the studies suggested that the 1-aryl-3-{4-[(pyridin-2-ylmethyl)thio]phenyl}urea skeleton might be regarded as new chemotypes for designing effective antiproliferative agents.

scholarly journals Design, Synthesis, and Biological Evaluation of Novel N-Acylhydrazone Bond Linked Heterobivalent β-Carbolines as Potential Anticancer Agents

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2950 ◽  
Author(s):  
Chen ◽  
Guo ◽  
Ma ◽  
Chen ◽  
Fan ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Chorioallantoic Membrane ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
In Vivo Model ◽  
Ic50 Values

Utilizing a pharmacophore hybridization approach, we have designed and synthesized a novel series of 28 new heterobivalent β-carbolines. The in vitro cytotoxic potential of each compound was evaluated against the five cancer cell lines (LLC, BGC-823, CT-26, Bel-7402, and MCF-7) of different origin—murine and human, with the aim of determining the potency and selectivity of the compounds. Compound 8z showed antitumor activities with half-maximal inhibitory concentration (IC50) values of 9.9 ± 0.9, 8.6 ± 1.4, 6.2 ± 2.5, 9.9 ± 0.5, and 5.7 ± 1.2 µM against the tested five cancer cell lines. Moreover, the effect of compound 8z on the angiogenesis process was investigated using a chicken chorioallantoic membrane (CAM) in vivo model. At a concentration of 5 μM, compound 8z showed a positive effect on angiogenesis. The results of this study contribute to the further elucidation of the biological regulatory role of heterobivalent β-carbolines and provide helpful information on the development of vascular targeting antitumor drugs.

Comparative analysis of XTT assay and xCELLigence system by measuring cytotoxicity of resveratrol in human cancer cell lines

2016 ◽  
Vol 41 (6) ◽  
Author(s):  
Harika Atmaca ◽  
Emir Bozkurt ◽  
Aslı Kısım ◽  
Rüçhan Uslu
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cultured Cells ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Dependent Manner ◽  
Xtt Assay ◽  
Concentration Dependent Manner ◽  
End Point

AbstractObjective:In vitro preliminary oncological and translational studies are mainly based on evaluating the cytotoxic effects of a specific compound on cultured cells. Resveratrol is a commercially available compound which is originally isolated from the roots of white hellebore and later fromMethods:XTT end point assay and real-time cell based xCELLigence system were used to evaluate cytotoxicity. Cytotoxicity results were verified by monitoring cells under phase-contrast microscope which were treated with ICResults:Resveratrol decreased cell viability in a time- and concentration-dependent manner in all cancer cell lines when tested by both the XTT assay and xCELLigence system. Standard deviations of the xCELLigence data were found to be lower than the data from XTT assay.Conclusion:The data from this study strongly imply that xCELLigence system has higher precision, more enlightening and more reproducible than XTT end point assay.

In Vitro Antitumor Evaluation of Some Hybrid Molecules Containing Coumarin and Quinolinone Moieties

2020 ◽  
Vol 19 (16) ◽  
pp. 2010-2018
Author(s):  
Youstina W. Rizzk ◽  
Ibrahim M. El-Deen ◽  
Faten Z. Mohammed ◽  
Moustafa S. Abdelhamid ◽  
Amgad I.M. Khedr
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Topoisomerase Ii ◽  
Cancer Cell Lines ◽  
Bax Protein ◽  
Hybrid Molecules ◽  
Mcf 7

Background: Hybrid molecules furnished by merging two or more pharmacophores is an emerging concept in the field of medicinal chemistry and drug discovery. Currently, coumarin hybrids have attracted the keen attention of researchers to discover their therapeutic capability against cancer. Objective: The present study aimed to evaluate the in vitro antitumor activity of a new series of hybrid molecules containing coumarin and quinolinone moieties 4 and 5 against four cancer cell lines. Materials and Methods: A new series of hybrid molecules containing coumarin and quinolinone moieties, 4a-c and 5a-c, were synthesized and screened for their cytotoxicity against prostate PC-3, breast MCF-7, colon HCT- 116 and liver HepG2 cancer cell lines as well as normal breast Hs-371 T. Results: All the synthesized compounds were assessed for their in vitro antiproliferative activity against four cancer cell lines and several compounds were found to be active. Further in vitro cell cycle study of compounds 4a and 5a revealed MCF-7 cells arrest at G2 /M phase of the cell cycle profile and induction apoptosis at pre-G1 phase. The apoptosis-inducing activity was evidenced by up-regulation of Bax protein together with the downregulation of the expression of Bcl-2 protein. The mechanism of cytotoxic activity of compounds 4a and 5a correlated to its topoisomerase II inhibitory activity. Conclusion: Hybrid molecules containing coumarin and quinolinone moieties represents a scaffold for further optimization to obtain promising anticancer agents.

Synthesis and Biological Evaluation of Novel 4-Phenylaminobenzofuro[2,3-d]pyrimidine Derivatives

2020 ◽  
Vol 42 (4) ◽  
pp. 564-564
Author(s):  
Ju liu Ju liu ◽  
Jun Li Jun Li ◽  
Jian tao Shi Jian tao Shi ◽  
Jie Li Jie Li ◽  
Xue chen Hao Xue chen Hao ◽  
...  
Keyword(s):  
Cell Lines ◽  
A549 Cells ◽  
Positive Control ◽  
Biological Evaluation ◽  
Dependent Manner ◽  
Pyrimidine Derivatives ◽  
Concentration Dependent Manner ◽  
Ic50 Value ◽  
Synthesis And Biological Evaluation

A series of novel 4-phenylaminobenzofuro[2,3-d]pyrimidine derivatives had been prepared and assessed for their in vitro antiproliferative activities against three lung cancer cell lines (A549, H460 and H1975). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activities. Among them, compound 8f exhibited remarkable inhibitory activity against A549 and H460 cell lines with IC50 value of 2.54 μM and 2.68 μM, respectively, which was comparable to that of the positive control sorafenib (IC50 = 2.69 μM for A549 and 3.71 μM for H460). AO/EB staining suggests that compound 8f could induce apoptosis in A549 cells. Furthermore, cell cycle analyses show that compound 8f increased G0/G1 A549 cells arrest in a concentration-dependent manner. The preliminary structure-activity relationships (SARs) studies indicated that mono-electron-withdrawing groups (mono-EWGs) on the phenyl ring are positive on the antitumor activity.

Novel N-bridged pyrazole-1-carbothioamides with potential antiproliferative activity: design, synthesis, in vitro and in silico studies

2021 ◽  
Vol 13 (20) ◽  
pp. 1743-1766
Author(s):  
Islam H El Azab ◽  
Essa M Saied ◽  
Alaa A Osman ◽  
Amir E Mehana ◽  
Hosam A Saad ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
In Silico ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Molecular Docking Study ◽  
In Silico Studies

Thiazole-substituted pyrazole is an important structural feature of many bioactive compounds, including antiviral, antitubercular, analgesic and anticancer agents. Herein we describe an efficient and facile approach for the synthesis of two series of 36 novel N-bridged pyrazole-1-phenylthiazoles. The antiproliferative activity of a set of representative compounds was evaluated in vitro against different human cancer cell lines. Among the identified compounds, compound 18 showed potent anticancer activity against the examined cancer cell lines. The in silico molecular docking study revealed that compound 18 possesses high binding affinity toward both SK1 and CDK2. Overall, these results indicate that compound 18 is a promising lead anticancer compound which may be exploited for development of antiproliferative drugs.

scholarly journals Isolation, Synthesis and Biological Evaluation of Phenylpropanoids from the Rhizomes of Alpania galanga

2013 ◽  
Vol 8 (12) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Sumit S Chourasiya ◽  
Eppakayala Sreedhar ◽  
K. Suresh Babu ◽  
Nagula Shankaraiah ◽  
V. Lakshma Nayak ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Colon Cancer ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Kinetic Resolution ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Biological Evaluation

Bioactivity guided investigation of the DCM: MeOH (1:1) extract from the rhizomes of Alpinia galanga led to the isolation of phenylpropanoids (1–9) and their structures were established by 1H NMR, 13C NMR, IR and LC-MS/MS. These compounds have been evaluated for their in vitro anticancer activity against the human cancer cell lines A549 (lung cancer), Colo-205 (colon cancer), A431 (skin cancer), NCI H460 (lung cancer), PC-3 (prostate cancer), and HT-29 (colon cancer). Compounds 4 and 9 showed potent anticancer activity (ranging from 1.3–19.7 μg/mL) against all the tested cancer cell lines. In addition, an asymmetric synthesis of acetoxychavicol acetate (1) and trans-p-coumaryl alcohol (4) has been accomplished in six steps starting from readily available p-hydroxybenzaldehyde for the first time. Grignard reaction and Sharpless kinetic resolution reactions were utilized as the key steps to install the basic core.

scholarly journals Some Wild Edible Mushroom Anticancer Activity Against Prostate Cell Lines

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 40
Author(s):  
Hatice Bekci ◽  
Mustafa Cam ◽  
Ahmet Cumaoglu
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Prostate Cancer Cell Lines ◽  
Prostate Cell

Prostate cancer is one of the cause of mortality and morbidity in men. High nutritional quality mushrooms have been consumed as food for a long time and Thanks to their bioactive components, they can be used in many fields such as pharmaceuticals, cosmetic products, dietary supplements and functional food production. The purpose of the research was to evaluate these derivatives against in vitro to obtain novel specific and effective anticancer agents against prostate cancer. In the study, Amanita caesarea, Sparassis crispa, Lepista nuda, Auricularia auricula, Tricholoma terreum and Lentinus tigrinus fungi were used. Anticancer activities of the compounds were evaluated in vitro by using MTT method against PC-3 and DU-143 (androgen-independent human prostate cancer cell lines) prostate cancer cell lines. Cisplatin was used as the positive sensitivity reference standard. The most effective among these fungus species biological activity against PC3 cancer cell line (IC50 = 327.34 µM), against DU-145 (IC50 = 459.19 µM).

scholarly journals Synthesis and Biological Evaluation of New Antitubulin Agents Containing 2-(3′,4′,5′-trimethoxyanilino)-3,6-disubstituted-4,5,6,7-tetrahydrothieno[2,3-c]pyridine Scaffold

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1690
Author(s):  
Romeo Romagnoli ◽  
Filippo Prencipe ◽  
Paola Oliva ◽  
Barbara Cacciari ◽  
Jan Balzarini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mononuclear Cells ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Pyridine Derivative ◽  
Tubulin Polymerization ◽  
Dependent Manner

Two novel series of compounds based on the 4,5,6,7-tetrahydrothieno[2,3-c]pyridine and 4,5,6,7-tetrahydrobenzo[b]thiophene molecular skeleton, characterized by the presence of a 3′,4′,5′-trimethoxyanilino moiety and a cyano or an alkoxycarbonyl group at its 2- or 3-position, respectively, were designed, synthesized, and evaluated for antiproliferative activity on a panel of cancer cell lines and for selected highly active compounds, inhibition of tubulin polymerization, and cell cycle effects. We have identified the 2-(3′,4′,5′-trimethoxyanilino)-3-cyano-6-methoxycarbonyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivative 3a and its 6-ethoxycarbonyl homologue 3b as new antiproliferative agents that inhibit cancer cell growth with IC50 values ranging from 1.1 to 4.7 μM against a panel of three cancer cell lines. Their interaction with tubulin at micromolar levels leads to the accumulation of cells in the G2/M phase of the cell cycle and to an apoptotic cell death. The cell apoptosis study found that compounds 3a and 3b were very effective in the induction of apoptosis in a dose-dependent manner. These two derivatives did not induce cell death in normal human peripheral blood mononuclear cells, suggesting that they may be selective against cancer cells. Molecular docking studies confirmed that the inhibitory activity of these molecules on tubulin polymerization derived from binding to the colchicine site.

scholarly journals Degalactotigonin, a Steroidal Glycoside from Solanum nigrum, Induces Apoptosis and Cell Cycle Arrest via Inhibiting the EGFR Signaling Pathways in Pancreatic Cancer Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Hoang Le Tuan Anh ◽  
Phuong Thao Tran ◽  
Do Thi Thao ◽  
Duong Thu Trang ◽  
Nguyen Hai Dang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Solanum Nigrum ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cycle Arrest

Degalactotigonin (1) and three other steroidal compounds solasodine (2), O-acetyl solasodine (3), and soladulcoside A (4) were isolated from the methanolic extract of Solanum nigrum, and their chemical structures were elucidated by spectroscopic analyses. The isolated compounds were evaluated for cytotoxic activity against human pancreatic cancer cell lines (PANC1 and MIA-PaCa2) and lung cancer cell lines (A549, NCI-H1975, and NCI-H1299). Only degalactotigonin (1) showed potent cytotoxicity against these cancer cell lines. Compound 1 induced apoptosis in PANC1 and A549 cells. Further study on its mechanism of action in PANC1 cells demonstrated that 1 significantly inhibited EGF-induced proliferation and migration in a concentration-dependent manner. Treatment of PANC1 cells with degalactotigonin induced cell cycle arrest at G0/G1 phase. Compound 1 induced downregulation of cyclin D1 and upregulation of p21 in a time- and concentration-dependent manner and inhibited EGF-induced phosphorylation of EGFR, as well as activation of EGFR downstream signaling molecules such as Akt and ERK.

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