Design and Microwave Synthesis of New (5Z) 5-Arylidene-2-thioxo-1,3-thiazolinidin-4-one and (5Z) 2-Amino-5-arylidene-1,3-thiazol-4(5H)-one as New Inhibitors of Protein Kinase DYRK1A

Here, we report on the synthesis of libraries of new 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones 3 (twenty-two compounds) and new 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones 5 (twenty-four compounds) with stereo controlled Z-geometry under microwave irradiation. The 46 designed final compounds were tested in order to determine their activity against four representative protein kinases (DYR1A, CK1, CDK5/p25, and GSK3α/β). Among these 1,3-thiazolidin-4-ones, the molecules (5Z) 5-(4-hydroxybenzylidene)-2-thioxo-1,3-thiazolidin-4-one 3e (IC50 0.028 μM) and (5Z)-5-benzo[1,3]dioxol-5-ylmethylene-2-(pyridin-2-yl)amino-1,3-thiazol-4(5H)-one 5s (IC50 0.033 μM) were identified as lead compounds and as new nanomolar DYRK1A inhibitors. Some of these compounds in the two libraries have been also evaluated for their in vitro inhibition of cell proliferation (Huh7 D12, Caco2, MDA-MB 231, HCT 116, PC3, and NCI-H2 tumor cell lines). These results will enable us to use the 1,3-thiazolidin-4-one core as pharmacophores to develop potent treatment for neurological or oncological disorders in which DYRK1A is fully involved.

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Inhibition of Tumor Cell Proliferation In Vitro by Benzamide Derivatives

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.997.225 ◽

2014 ◽

Vol 997 ◽

pp. 225-228 ◽

Cited By ~ 1

Author(s):

Yan Ling Wu ◽

Li Wen Shen ◽

Yan Ping Ding ◽

Yoshimasa Tanaka ◽

Wen Zhang

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Malignant Tumors ◽

Dependent Manner ◽

Tumor Cell Lines ◽

Lead Compounds ◽

Proliferative Effect ◽

Benzamide Derivatives

Benzamide derivatives have been shown to have antitumor activity in various tumor cell lines in vitro as well as in vivo. In this study, we examined the anti-proliferative effect of four benzamide derivativeson Hela, H7402, and SK-RC-42 tumor cell lines in vitro by means of Real-Time cell assay (RTCA), and found that four benzamide derivatives suppressed proliferation of tumor cells in a time-and dose-dependent manner. The anti-proliferative activity of benzamide derivatives demonstrated that theycould be promising lead compounds for developing therapeutic agents for malignant tumors.

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An Automated Image Capture and Quantitation Approach to Identify Proteins Affecting Tumor Cell Proliferation

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057103262842 ◽

2004 ◽

Vol 9 (3) ◽

pp. 216-222 ◽

Cited By ~ 11

Author(s):

Kaumudi M. Bhawe ◽

Robert A. Blake ◽

Douglas O. Clary ◽

Peter M. Flanagan

Keyword(s):

Cell Proliferation ◽

Tumor Cell ◽

Cell Lines ◽

Kinase Inhibitor ◽

Enzyme Linked Immunosorbent Assay ◽

Functional Assay ◽

Tumor Cell Lines ◽

Tumor Cell Proliferation ◽

Adenoviral Infection

To facilitate the characterization of proteins that negatively regulate tumor cell proliferation in vitro, the authors have implemented a high-throughput functional assay that measures S-phase progression of tumor cell lines. For 2 tumor cell lines—human melanoma A375 and human lung carcinoma A549—conditions were established using the cyclin-dependent kinase inhibitor, p27kip; the tumor suppressor p53, a kinase-inactive allele of the cell cycle-regulated serine/threonine kinase Aurora2; and the G1/S drug block, aphidicolin. For screening purposes, gene libraries were delivered by adenoviral infection. Cells were fixed and labeled by immunocytochemistry, and an automated image acquisition and analysis package on a Cellomics ArrayScan®II was used to quantify the effects of these treatments on cell proliferation. The assay can be used to identify novel proteins involved in proliferation and serves as a more robust, reproducible, and sensitive alternative to enzyme-linked immunosorbent assay (ELISA)-based technologies.

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Preliminary in vitro evaluation of the anti-proliferative activity of guanylhydrazone derivatives

Acta Pharmaceutica ◽

10.1515/acph-2016-0015 ◽

2016 ◽

Vol 66 (1) ◽

pp. 129-137 ◽

Cited By ~ 7

Author(s):

Paulo H. B. França ◽

Edeildo F. Da Silva-Júnior ◽

Pedro G. V. Aquino ◽

Antônio E. G. Santana ◽

Jamylle N. S. Ferro ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Anticancer Agents ◽

Human Tumor ◽

Tetrazolium Salt ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Lead Compounds

Abstract Guanylhydrazones have shown promising antitumor activity in preclinical tumor models in several studies. In this study, we aimed at evaluating the cytotoxic effect of a series of synthetic guanylhydrazones. Different human tumor cell lines, by including HCT-8 (colon carcinoma), MDA-MB-435 (melanoma) and SF-295 (glioblastoma) were continuous exposed to guanylhydrazone derivatives for 72 hours and growth inhibition of tumor cell lines and macrophages J774 was measured using tetrazolium salt (MTT) assay. Compounds 7, 11, 16 and 17 showed strong cytotoxic activity with IC50 values lower than 10 μmol L−1 against four tumor cell lines. Among them, 7 was less toxic to non-tumor cells. Finally, obtained data suggest that guanylhydrazones may be regarded as potential lead compounds for the design of novel anticancer agents.

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5-Acetamido-1-(methoxybenzyl) isatin inhibits tumor cell proliferation, migration, and angiogenesis

RSC Advances ◽

10.1039/c9ra07002h ◽

2019 ◽

Vol 9 (63) ◽

pp. 36690-36698

Author(s):

Qian Zhang ◽

Ying Fu ◽

Yufan Zhao ◽

Shanshan Cui ◽

Jing Wang ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Cell ◽

Cell Lines ◽

Tumor Cell Lines ◽

Tumor Cell Proliferation

5-Acetamido-1-(methoxybenzyl) isatin inhibited the proliferation, migration, and angiogenesis of several tumor cell lines in vitro.

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Comparative Assay of 2D and 3D Cell Culture Models: Proliferation, Gene Expression and Anticancer Drug Response

Current Pharmaceutical Design ◽

10.2174/1381612824666180404152304 ◽

2018 ◽

Vol 24 (15) ◽

pp. 1689-1694 ◽

Cited By ~ 25

Author(s):

Aline G. Souza ◽

Isaura Beatriz B. Silva ◽

Esther Campos-Fernandez ◽

Leticia S. Barcelos ◽

Jessica Brito Souza ◽

...

Keyword(s):

Gene Expression ◽

Cell Culture ◽

Cell Proliferation ◽

Tumor Cell ◽

3D Cell Culture ◽

Tumor Cell Lines ◽

2D And 3D ◽

Prostate Tumor Cell

Background: In vitro tests allow establishing experimental variables. However, in vitro results cannot be extrapolated to in vivo tests. Considering that three-dimensional (3D) culture has been one of the best ways to portray the in vivo system of most cell types, it is possible to carry out assays with a great clinical relevance for the analysis of the screening, action and resistance of antitumor drugs. Objective: Thus, the objective of the present study was to compare between 2D and 3D cell culture forms to conclude which is the most suitable model for preclinical in vitro drug testing. Method: We evaluated the proliferation, genetic expression and chemoresistance of prostate tumor cell lines, PC- 3, LNCaP and DU145. Prostate tumor cell lines PC-3, LNCaP and DU145 were treated with the antineoplastic drugs paclitaxel and docetaxel and evaluated with cytotoxicity, cell proliferation and gene expression assays in 2D and magnetic 3D bioprinting cultures. Results: Lower cell proliferation rate, more resistance to paclitaxel and docetaxel and altered gene expression profile was shown in 3D cell culture comparing with its 2D counterpart. Conclusion: 3D cell culture exhibited a more similar behavior to in vivo systems, being a promising and more reliable tool for the development of new drugs.

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Processing of Proaugurin Is Required to Suppress Proliferation of Tumor Cell Lines

Molecular Endocrinology ◽

10.1210/me.2010-0389 ◽

2011 ◽

Vol 25 (5) ◽

pp. 776-784 ◽

Cited By ~ 23

Author(s):

Akihiko Ozawa ◽

Adam N. Lick ◽

Iris Lindberg

Keyword(s):

Cell Proliferation ◽

Tumor Cell ◽

Cell Lines ◽

Secretory Pathway ◽

Secretory Granules ◽

Major Product ◽

Metabolic Labeling ◽

Tumor Cell Lines ◽

Suppress Cell Proliferation

Abstract Augurin is a secretory molecule produced in pituitary, thyroid, and esophagus and implicated in a wide array of physiological processes, from ACTH release to tumor suppression. However, the specific proaugurin-derived peptides present in various cell types are not yet known. In order to shed light on the posttranslational modifications required for biological activity, we here describe the posttranslational processing of proaugurin in AtT-20 and Lovo cells and identify proaugurin-derived products generated by convertases. In vitro cleavage of proaugurin with proprotein convertases produced multiple peptides, including a major product with a mass of 9.7 kDa by mass spectrometry. Metabolic labeling of C-terminally tagged proaugurin in AtT-20 and AtT-20/PC2 cells resulted in a major 15-kDa tagged form on SDS-PAGE, which likely corresponds to the 9.7-kDa in vitro fragment, with the added tag, its linker, and posttranslational modification(s). The secretion of neither proaugurin nor this cleavage product was stimulated by forskolin, indicating its lack of storage in regulated secretory granules and lack of cleavage by PC2. Incubation of cells with the furin inhibitor nona-d-arginine resulted in impaired cleavage of proaugurin, whereas metalloprotease inhibitors did not affect proaugurin proteolysis. These data support the idea that proaugurin is cleaved by furin and secreted via the constitutive secretory pathway. Interestingly, proaugurin was sulfated during trafficking; sulfation was completely inhibited by brefeldin A. Proliferation assays with three different tumor cell lines demonstrated that only furin-cleaved proaugurin could suppress cell proliferation, suggesting that proteolytic cleavage is a posttranslational requirement for proaugurin to suppress cell proliferation.

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Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190730164952 ◽

2020 ◽

Vol 17 (4) ◽

pp. 512-517

Author(s):

Ognyan Ivanov Petrov ◽

Yordanka Borisova Ivanova ◽

Mariana Stefanova Gerova ◽

Georgi Tsvetanov Momekov

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Biological Activities ◽

Human Tumor ◽

Mannich Bases ◽

In Vitro Cytotoxicity ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

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Cytotoxic Effect of Brassica oleracea Extract on two Tumor Cell Lines in vitro

Journal of Al-Nahrain University-Science ◽

10.22401/jnus.16.1.20 ◽

2013 ◽

Vol 16 (1) ◽

pp. 137-142

Author(s):

Farooq I. Mohammed ◽

◽

Farah T. Abdullah ◽

Shaimaa Y. Abdulfttah ◽

◽

...

Keyword(s):

Tumor Cell ◽

Brassica Oleracea ◽

Cell Lines ◽

Cytotoxic Effect ◽

Tumor Cell Lines

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Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽

10.3390/biomedicines9010092 ◽

2021 ◽

Vol 9 (1) ◽

pp. 92

Author(s):

Bashir Lawal ◽

Yen-Lin Liu ◽

Ntlotlang Mokgautsi ◽

Harshita Khedkar ◽

Maryam Rachmawati Sumitra ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Cancer Cell ◽

Human Tumor ◽

Cancer Cell Lines ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

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