scholarly journals Synthesis and cytotoxicity of novel oxindoles dispiro derivatives with thiohydantoin and adamantane fragments

2019 ◽  
Author(s):  
Maxim E Kukushkin ◽  
Dmitriy A Skvortsov ◽  
Marina A Kalinina ◽  
Viktor A Tafeenko ◽  
Vladimir V Burmistrov ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
A549 Cell ◽  
Azomethine Ylides ◽  
Dipolar Cycloaddition ◽  
A549 Cell Line ◽  
One Pot ◽  
P53 Activation

An effective and highly regio- and diastereoselective one-pot synthesis of two type of dispiro heterocyclic systems (2-thioxodispiro[imidazolidine-4,3'-pyrrolidine-2',3''-indoline]-2'',5-diones and 2-thioxodispiro[imidazolidine-4,3'-pyrrolidine-4',3''-indoline]-2'',5-diones) comprising pyrrolidinyloxindole, thiohydantoin and adamantane moieties have been developed based on a 1,3-dipolar cycloaddition of azomethine ylides, generated from isatin and sarcosine or formaldehyde and sarcosine, to adamantine-containing electron-deficient alkenes. Several molecules have demonstrated a considerable cytotoxicity against and A549, HEK293T, MCF7 and VA13 cancer cell lines. The possible mechanism of anticancer activity of synthesised compounds based on literature data may be the inhibition of p53/MDM2 interaction, however, we did not observe significant p53 activation using a reporter construction in A549 cell line in a relevant concentration range.

scholarly journals Stereoselective Synthesis of the Di-Spirooxindole Analogs Based Oxindole and Cyclohexanone Moieties as Potential Anticancer Agents

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6305
Author(s):  
Abdullah Mohammed Al-Majid ◽  
M. Ali ◽  
Mohammad Shahidul Islam ◽  
Saeed Alshahrani ◽  
Abdullah Saleh Alamary ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Stereoselective Synthesis ◽  
Cancer Cell Lines ◽  
Azomethine Ylides ◽  
Active Member ◽  
One Pot

A new series of di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were synthesized. Initially, azomethine ylides were generated via reaction of the substituted isatins 3a–f (isatin, 3a, 6-chloroisatin, 3b, 5-fluoroisatin, 3c, 5-nitroisatin, 3d, 5-methoxyisatin, 3e, and 5-methylisatin, 3f, and (2S)-octahydro-1H-indole-2-carboxylic acid 2, in situ azomethine ylides reacted with the cyclohexanone based-chalcone 1a–f to afford the target di-spirooxindole compounds 4a–n. This one-pot method provided diverse structurally complex molecules, with biologically relevant spirocycles in a good yields. All synthesized di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were evaluated for their anticancer activity against four cancer cell lines, including prostate PC3, cervical HeLa, and breast (MCF-7, and MDA-MB231) cancer cell lines. The cytotoxicity of these di-spirooxindole analogs was also examined against human fibroblast BJ cell lines, and they appeared to be non-cytotoxic. Compound 4b was identified as the most active member of this series against prostate cancer cell line PC3 (IC50 = 3.7 ± 1.0 µM). The cyclohexanone engrafted di-spirooxindole analogs 4a and 4l (IC50 = 7.1 ± 0.2, and 7.2 ± 0.5 µM, respectively) were active against HeLa cancer cells, whereas NO2 substituted isatin ring and meta-fluoro-substituted (2E,6E)-2,6-dibenzylidenecyclohexanone containing 4i (IC50 = 7.63 ± 0.08 µM) appeared to be a promising agent against the triple negative breast cancer MDA-MB231 cell line. To explore the plausible mechanism of anticancer activity of di-spirooxindole analogs, molecular docking studies were investigated which suggested that spirooxindole analogs potentially inhibit the activity of MDM2.

scholarly journals Correction: Gobinath, P., et al. Grindstone Chemistry: Design, One-Pot Synthesis, and Promising Anticancer Activity of Spiro[acridine-9,2′-indoline]-1,3,8-trione Derivatives against the MCF-7 Cancer Cell Line. Molecules 2020, 25, 5862

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1131
Author(s):  
Perumal Gobinath ◽  
Ponnusamy Packialakshmi ◽  
Ali Daoud ◽  
Saud Alarifi ◽  
Akbar Idhayadhulla ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
One Pot ◽  
One Pot Synthesis ◽  
Mcf 7

In the original article [...]

scholarly journals Promising Anticancer Activity of [Bis(1,8-quinolato)palladium (II)] Alone and in Combination

2020 ◽  
Author(s):  
Md. Nur Alam ◽  
Mohammad Moni ◽  
Jun Yu ◽  
Philip Beale ◽  
Peter Turner ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Anticancer Activity ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumour Activity ◽  
Epigallocatechin Gallate ◽  
Cancer Cell Line ◽  
Resistant Cell ◽  
Colorectal Cancer Cell Line

Abstract Due to similar coordination chemistry of palladium and platinum, a large number of palladium compounds too have been investigated for their anticancer activity. In the present study we describe synthesis, characterization and anticancer activity of palladium complex [Bis(1,8-quinolato)palladium (II)], coded as NH3 against seven different cancer cell lines. NH3 is found to have higher antitumour activity than cisplatin against both parent ovarian A2780 cell line and cisplatin-resistant cell lines. Also, NH3 has the lowest IC50 value against HT-29 colorectal cancer cell line. The higher antitumour activity of NH3 is due to the presence of bulky 8-hydroxy-quinoline ligand thus reducing its reactivity. Proteomic study has identified significantly expressed proteins which have been validated through bioinformatics. NH3 has been found to be less toxic than cisplatin at 2.5 mg/kg and 5 mg/kg dosages on mice models. Binary combinations of NH3 with curcumin and epigallocatechin gallate (EGCG) have demonstrated dose and sequence dependent synergism in ovarian and colorectal cancer models. All of the preclinical studies indicate promising therapeutic potentiality of NH3 [Bis(1,8-quinolato)palladium (II) ] as an anticancer drug.

Dynamic interconversion between CD90+ and CD90− cancer cell populations in lung cancer A549 cell line

2018 ◽  
Vol 14 (5) ◽  
pp. 1822
Author(s):  
Wai-Kin Yu ◽  
Yuen-San Chan ◽  
Weimao Wang ◽  
Chi-chun Fong ◽  
Tak-Chun Yip ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
A549 Cell ◽  
Cell Populations ◽  
A549 Cell Line ◽  
Lung Cancer A549 Cell

scholarly journals Evaluation of Anticancer Activity of Olmesartan and Ramipril On A549 Cell Line

2018 ◽  
Vol 11 (3) ◽  
pp. 1351-1357 ◽  
Author(s):  
E Gayathri ◽  
K. Punnagai ◽  
D. Darling Chellathai
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Anticancer Activity ◽  
Cell Line ◽  
A549 Cell ◽  
Enzyme Inhibitor ◽  
A549 Cell Line ◽  
Ic50 Values

Angiotensin Converting Enzyme Inhibitor (ACEI) and Angiotensin II type 1 receptor antagonist (ARBs) are the most efficient cardiovascular drugs and exhibited efficient cytostatic activity in vitro in many malignant and normal cells1.OBJECTIVE: This study aims to assess the anticancer activity of these two drugs in a dose dependant manner using A549 cell line through MTT assay and Cell cycle analysis.. MATERIALS AND METHODS: Ramipril and Olmesartan were added to A549 at various concentrations ranging from 10⁻⁶ to 10mM.The dot plot of the cytotoxicity results were used to extrapolate the IC50 values. The dot plot of flow cytometry results were used to extrapolate the DNA percentage in phases of cell cycle. The plates were read at 570 nm by using a PERCLIN ELMER (multimode reader). Measurements for concentration required for 50% inhibition was noted. RESULTS: Ramipril and Olmesartan were added to A549 at various concentrations ranging from 10⁻⁶ to 10mM.The dot plot of the cytotoxicity results were used to extrapolate the IC50 values. The dot plot of flow cytometry results were used to extrapolate the DNA percentage in phases of cell cycle.

scholarly journals RNAseq reveals extensive metabolic disruptions in the sensitive SF-295 cell line treated with schweinfurthins

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
J. S. Weissenrieder ◽  
J. D. Weissenkampen ◽  
J. L. Reed ◽  
M. V. Green ◽  
C. Zheng ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
A549 Cell ◽  
Protein Metabolism ◽  
A549 Cells ◽  
Hedgehog Pathway ◽  
Late Time ◽  
A549 Cell Line ◽  
Significant Interaction Effect

AbstractThe schweinfurthin family of natural compounds exhibit a unique and potent differential cytotoxicity against a number of cancer cell lines and may reduce tumor growth in vivo. In some cell lines, such as SF-295 glioma cells, schweinfurthins elicit cytotoxicity at nanomolar concentrations. However, other cell lines, like A549 lung cancer cells, are resistant to schweinfurthin treatment up to micromolar concentrations. At this time, the precise mechanism of action and target for these compounds is unknown. Here, we employ RNA sequencing of cells treated with 50 nM schweinfurthin analog TTI-3066 for 6 and 24 h to elucidate potential mechanisms and pathways which may contribute to schweinfurthin sensitivity and resistance. The data was analyzed via an interaction model to observe differential behaviors between sensitive SF-295 and resistant A549 cell lines. We show that metabolic and stress-response pathways were differentially regulated in the sensitive SF-295 cell line as compared with the resistant A549 cell line. In contrast, A549 cell had significant alterations in response genes involved in translation and protein metabolism. Overall, there was a significant interaction effect for translational proteins, RNA metabolism, protein metabolism, and metabolic genes. Members of the Hedgehog pathway were differentially regulated in the resistant A549 cell line at both early and late time points, suggesting a potential mechanism of resistance. Indeed, when cotreated with the Smoothened inhibitor cyclopamine, A549 cells became more sensitive to schweinfurthin treatment. This study therefore identifies a key interplay with the Hedgehog pathway that modulates sensitivity to the schweinfurthin class of compounds.

Design, Synthesis, Biological Evaluation and In Silico Studies of Few Novel 2-Substituted Benzothiazole Derivatives as Potential EGFR Inhibitors

2019 ◽  
Vol 16 (8) ◽  
pp. 961-971 ◽  
Author(s):  
Muhammad Mubeen ◽  
Suvarna Ganesh Kini ◽  
Avinash Kumar ◽  
Karkala Sreedhara Ranganath Pai
Keyword(s):  
Anticancer Activity ◽  
Cell Line ◽  
A549 Cell ◽  
Biological Evaluation ◽  
Maximum Activity ◽  
A549 Cell Line ◽  
Allosteric Site ◽  
Benzothiazole Derivatives ◽  
Ic50 Value ◽  
Mcf 7

Background: There is a great unmet medical need for new anticancer small molecule therapeutics. Exhaustive literature review suggests that benzothiazole derivatives have good potential to exhibit anticancer activity. Compounds that inhibit the kinase activity of EGFR are of potential interest as new antitumor agent. Objective: To design, synthesize and carry out in silico along with biological evaluation of 2- substituted benzothiazole compounds with EGFR inhibitory activity. Methods: Benzothiazole derivatives designed from molecular docking method for potential EGFR tyrosine kinase inhibition have been synthesized based on the docking results and characterized. Insilico studies were carried out to understand the mode of EGFR enzyme inhibition by our molecules. As a preliminary study, these compounds were first screened for antioxidant activity and then for anticancer activity against MCF-7 cell lines and A549 cell line. Results: Compound B5 showed potent anticancer activity on MCF-7 cell line with IC50 value of 9.7µM and compound B8 showed significant anticancer activity on A549 cell line with IC50 value of 49.7μM in comparison with the standard drug Doxorubicin (IC50 = 1.4µM on MCF-7 and 1.0µM on A549 cell lines). In EGFR inhibitory activity B8 showed maximum activity on A549 cell line by inactivating 69.10% of EGFR phosphorylation and B7 showed maximum activity on MCF-7 cell line by inactivating 41.90% of EGFR phosphorylation in comparison with the reference drug Gefitinib. Molecular dynamics simulation studies suggest that benzothiazole derivative could also bind to allosteric site and inhibit the EGFR enzyme activity. Conclusion: Reported compounds have shown potent anticancer activity through EGFR inhibition by possibly binding at allosteric site.

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