scholarly journals Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-azaspiro[4,5]deca-6,9-diene-3,8-dione Derivatives

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 936
Author(s):  
Ze Yang ◽  
Qiu Zhong ◽  
Shilong Zheng ◽  
Guangdi Wang ◽  
Ling He
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Oxidative Cyclization ◽  
Human Lung Cancer ◽  
Reaction Conditions ◽  
Promising Candidate ◽  
Metal Catalyzed ◽  
Further Development

A series of novel 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones were designed and synthesized by using 4-aminophenol and α-glycolic acid or lactic acid as starting materials in three or four steps. The key step is the metal-catalyzed oxidative cyclization of the amide to 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones (10a and 10b), the reaction conditions of which are investigated and optimized. The anticancer activity of 17 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-dione derivatives was evaluated. Preliminary results showed that 15 compounds have moderate to potent activity against human lung cancer A549, human breast cancer MDA-MB-231, and human cervical cancer HeLa cancer cell lines. Among them, compounds 11b and 11h were the most potent against A549 cell line with 0.18 and 0.19 µM of IC50, respectively; compounds 11d, 11h, and 11k showed the most potent cytotoxicity against MDA-MB-231 cell line with 0.08, 0.08, and 0.09 µM of IC50, respectively, while the activities of 11h, 11k, and 12c against HeLa cell line were the most potent with 0.15, 0.14, and 0.14 µM of IC50, respectively. Compound 11h is a promising candidate for further development, which emerged as the most effective compound overall against the three tested cancer cell lines.

Antiproliferative Activity of Protopine Extract from Fumaria agraria Against Human Lung Cancer Cell Lines

2021 ◽  
Author(s):  
K. Bougoffa-Sadaoui ◽  
F. Maiza-Benabdesselam ◽  
H. Ouadid-Ahidouch
Keyword(s):  
Lung Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Lung ◽  
Cancer Cell Lines ◽  
Human Lung Cancer ◽  
Lung Cancer Cell ◽  
Antitumor Effects ◽  
Fumaria Agraria

Little information is reported on the antitumor effects of isoquinoline alkaloids, particularly protopine, a major component of Fumaria agraria, on lung cancer. The purpose of our study is to determine the cytotoxic effect of protopine from an extraction by fractionation of the aerial part of Fumaria agraria on two lung cancer cell lines, NCI-H23 and NCI-H460. The basic fraction containing protopine (60.7%) has cytotoxicity to the two lung cancer cell lines studied here. The cell line NCI-H460 is more sensitive after 72 h of treatment by protopine with an IC50 of 08.5 ± 0.09 μMthan the cell line NCI-H23 (IC50 = 14.8 ± 0.03 μM).

scholarly journals Synthesis and Cytotoxicities of Novel Podophyllotoxin Xyloside Derivatives

2019 ◽  
Vol 14 (7) ◽  
pp. 1934578X1986066
Author(s):  
Cheng-Ting Zi ◽  
Liu Yang ◽  
Bang-Lei Zhang ◽  
Yan Li ◽  
Zhong-Tao Ding ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Human Cancer Cell ◽  
Promising Candidate ◽  
Human Cancer Cell Lines ◽  
Diphenyltetrazolium Bromide ◽  
Further Development ◽  
Mcf 7

Novel podophyllotoxin xyloside derivatives 8 to 11 were synthesized and evaluated for their cytotoxicities against a panel of 5 human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using [3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays. These derivatives showed good to moderate activities, with compound 9 having an IC50 value of 4.42 μM against the A-549 cell line. Overall, compound 9 might be a promising candidate for further development.

Synthesis and Anti-Proliferative Evaluations of New Heterocyclic Derivatives using 5,6,8,9-tetrahydropyrazolo[5,1-b]quinazolin-7(3H)-one Derivatives Derived from Cyclohexa-1,4-dione

2020 ◽  
Vol 20 ◽  
Author(s):  
Mahmoud A.A. Mahmoud ◽  
Meshari A. Alsharif ◽  
Rafat M. Mohareb
Keyword(s):  
Lung Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mtt Assay ◽  
Cancer Cell Lines ◽  
Positive Control ◽  
Human Lung Cancer ◽  
Wide Range ◽  
Target Molecules

Background: Recentlty pyrazoloquinazoline derivatives acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Through the market it was found that many pharmacological drugs containing the quinazoline nucleus were known. Objective: We are aiming in this work to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. The target molecules were obtained through the synthesis of a series of 5,6,8,9-tetrahydropyrazolo[5,1-b]quinazolin-7(3H)-one derivatives 4a-i using the multicomponent reactions of cyclohexan-1,4-dione (1), the 5-amino-4-(2-arylhydrazono)-4H-pyrazol-3-ol derivatives 2a-c the aromatic aldehydes 3a-c, respectively. The synthesized compounds were evaluated against c-Met kinase, PC-3 cell line and different kinds of cancer cell lines together with normal cell line, tyrosine kinases and Pim-1 kinase. Methods: Muticomponent reactions were adopted using compound 1 to get different 5,6,8,9- tetrahydropyrazolo[5,1-b]quinazolin-7(3H)-one derivatives which underwent further heterocyclization reactions. The c-Met kinase activity of all compounds was evaluated using Homogeneous TimeResolved Fluorescence (HTRF) assay taking foretinib as the positive control. . The anti-proliferative activity of all target compounds against the human prostatic cancer PC-3 cell line were measured using MTT assay using SGI-1776 as the reference drug. All the synthesized compounds were assessed the inhibitory activities against A549 (non-small cell lung cancer), H460 (human lung cancer), HT-29 (human colon cancer) and MKN-45 (human gastric cancer cancer) cancer cell lines together with foretinib as the positive control by a MTT assay. Results: Antiproliferative evaluations and c-Met kinase, Pim-1 kinse inhibitions were perform for the synthesized compounds where the varieties of substituent through the aryl ring and the thiophene moiety afforded compounds with high activities. Conclusion: The compounds with high antiprolifeative activity were tested toward c-Met and the results showed that compounds 4e, 4f, 4g, 4i, 6i, 6k, 6l, 8f, 8i, 10d, 10e, 10f, 10h, 12e, 12f, 12g, 12h, 12i, 14f, 14g, 14h and 14i were the most potent compounds. Further selection of compounds for the Fused Quinazoline Derivatives as Anticancer Agents Pim-1 kinase inhibition activity showed that compounds 4f, 6i, 6l, 8h, 8i,8g, 10d, 12i and 14f were the most active compounds to inhibit Pim-1.

ANTITUMOR EFFECT OF SUNITINIB AND BORTEZOMIB ON BREAST CANCER CELL LINE IN VITRO

2017 ◽  
Vol 63 (1) ◽  
pp. 141-145
Author(s):  
Yuliya Khochenkova ◽  
Eliso Solomko ◽  
Oksana Ryabaya ◽  
Yevgeniya Stepanova ◽  
Dmitriy Khochenkov
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Antitumor Effect ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Actual Problem

The discovery for effective combinations of anticancer drugs for treatment for breast cancer is the actual problem in the experimental chemotherapy. In this paper we conducted a study of antitumor effect of the combination of sunitinib and bortezomib against MDA-MB-231 and SKBR-3 breast cancer cell lines in vitro. We found that bortezomib in non-toxic concentrations can potentiate the antitumor activity of sunitinib. MDA-MB-231 cell line has showed great sensitivity to the combination of bortezomib and sunitinib in vitro. Bortezomib and sunitinib caused reduced expression of receptor tyrosine kinases VEGFR1, VEGFR2, PDGFRa, PDGFRß and c-Kit on HER2- and HER2+ breast cancer cell lines

Synthesis and Characterization of Quinoline-3-Carboxamide Derivatives as Inhibitors of the ATM Kinase

2020 ◽  
Vol 20 (23) ◽  
pp. 2070-2079
Author(s):  
Srimadhavi Ravi ◽  
Sugata Barui ◽  
Sivapriya Kirubakaran ◽  
Parul Duhan ◽  
Kaushik Bhowmik
Keyword(s):  
Western Blot ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Cancer Cell Lines ◽  
Atm Kinase ◽  
Cytotoxicity Studies

Background: The importance of inhibiting the kinases of the DDR pathway for radiosensitizing cancer cells is well established. Cancer cells exploit these kinases for their survival, which leads to the development of resistance towards DNA damaging therapeutics. Objective: In this article, the focus is on targeting the key mediator of the DDR pathway, the ATM kinase. A new set of quinoline-3-carboxamides, as potential inhibitors of ATM, is reported. Methods: Quinoline-3-carboxamide derivatives were synthesized and cytotoxicity assay was performed to analyze the effect of molecules on different cancer cell lines like HCT116, MDA-MB-468, and MDA-MB-231. Results: Three of the synthesized compounds showed promising cytotoxicity towards a selected set of cancer cell lines. Western Blot analysis was also performed by pre-treating the cells with quercetin, a known ATM upregulator, by causing DNA double-strand breaks. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. Finally, Western-Blot analysis confirmed the down-regulation of ATM in the cells. Additionally, the PTEN negative cell line, MDA-MB-468, was more sensitive towards the compounds in comparison with the PTEN positive cell line, MDA-MB-231. Cytotoxicity studies against 293T cells showed that the compounds were at least three times less toxic when compared with HCT116. Conclusion: In conclusion, these experiments will lay the groundwork for the evolution of potent and selective ATM inhibitors for the radio- and chemo-sensitization of cancer cells.

Synthesis, Anticancer Activity on Prostate Cancer Cell Lines and Molecular Modeling Studies of Flurbiprofen-Thioether Derivatives as Potential Target of MetAP (Type II)

2020 ◽  
Vol 16 (6) ◽  
pp. 735-749 ◽  
Author(s):  
Özgür Yılmaz ◽  
Burak Bayer ◽  
Hatice Bekçi ◽  
Abdullahi I. Uba ◽  
Ahmet Cumaoğlu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Modeling ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Prostate Cancer Cell Lines ◽  
Molecular Modeling Studies

Background:: Prostate cancer is still one of the serious causes of mortality and morbidity in men. Despite recent advances in anticancer therapy, there is a still need of novel agents with more efficacy and specificity in the treatment of prostate cancer. Because of its function on angiogenesis and overexpression in the prostate cancer, methionine aminopeptidase-2 (MetAP-2) has been a potential target for novel drug design recently. Objective:: A novel series of Flurbiprofen derivatives N-(substituted)-2-(2-(2-fluoro-[1,1'- biphenyl]-4-il)propanoyl)hydrazinocarbothioamide (3a-c), 4-substituted-3-(1-(2-fluoro-[1,1'-biphenyl]- 4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione (4a-d), 3-(substitutedthio)-4-(substituted-phenyl)- 5-(1-(2-fluoro-[1,1'-biphenyl]-4-yl)ethyl)-4H-1,2,4-triazole (5a-y) were synthesized. The purpose of the research was to evaluate these derivatives against MetAP-2 in vitro and in silico to obtain novel specific and effective anticancer agents against prostate cancer. Methods: The chemical structures and purities of the compounds were defined by spectral methods (1H-NMR, 13C-NMR, HR-MS and FT-IR) and elemental analysis. Anticancer activities of the compounds were evaluated in vitro by using MTS method against PC-3 and DU-143 (androgenindependent human prostate cancer cell lines) and LNCaP (androgen-sensitive human prostate adenocarcinoma) prostate cancer cell lines. Cisplatin was used as a positive sensitivity reference standard. Results:: Compounds 5b and 5u; 3c, 5b and 5y; 4d and 5o showed the most potent biological activity against PC3 cancer cell line (IC50= 27.1 μM, and 5.12 μM, respectively), DU-145 cancer cell line (IC50= 11.55 μM, 6.9 μM and 9.54 μM, respectively) and LNCaP cancer cell line (IC50= 11.45 μM and 26.91 μM, respectively). Some compounds were evaluated for their apoptotic caspases protein expression (EGFR/PI3K/AKT pathway) by Western blot analysis in androgen independent- PC3 cells. BAX, caspase 9, caspsase 3 and anti-apoptotic BcL-2 mRNA levels of some compounds were also investigated. In addition, molecular modeling studies of the compounds on MetAP-2 enzyme active site were evaluated in order to get insight into binding mode and energy. Conclusion:: A series of Flurbiprofen-thioether derivatives were synthesized. This study presented that some of the synthesized compounds have remarkable anticancer and apoptotic activities against prostate cancer cells. Also, molecular modeling studies exhibited that there is a correlation between molecular modeling and anticancer activity results.

Design, Synthesis, Molecular Docking, and Anticancer Evaluation of Pyrazole Linked Pyrazoline Derivatives with Carbothioamide Tail as EGFR Kinase Inhibitors

2020 ◽  
Vol 21 (1) ◽  
pp. 42-60
Author(s):  
Farah Nawaz ◽  
Ozair Alam ◽  
Ahmad Perwez ◽  
Moshahid A. Rizvi ◽  
Mohd. Javed Naim ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Kinase Assay ◽  
Cervix Uteri ◽  
Egfr Kinase

Background: The Epidermal Growth Factor Receptor (known as EGFR) induces cell differentiation and proliferation upon activation through the binding of its ligands. Since EGFR is thought to be involved in the development of cancer, the identification of new target inhibitors is the most viable approach, which recently gained momentum as a potential anticancer therapy. Objective: To assess various pyrazole linked pyrazoline derivatives with carbothioamide for EGFR kinase inhibitory as well as anti-proliferative activity against human cancer cell lines viz. A549 (non-small cell lung tumor), MCF-7 (breast cancer cell line), SiHa (cancerous tissues of the cervix uteri), and HCT-116 (colon cancer cell line). Methods: In vitro EGFR kinase assay, in vitro MTT assay, Lactate dehydrogenase release, nuclear staining (DAPI), and flow cytometry cell analysis. Results: Compounds 6h and 6j inhibited EGFR kinase at concentrations of 1.66μM and 1.9μM, respectively. Furthermore, compounds 6h and 6j showed the most potent anti-proliferative results against the A549 KRAS mutation cell line (IC50 = 9.3 & 10.2μM). Through DAPI staining and phase contrast microscopy, it was established that compounds 6h and 6j also induced apoptotic activity in A549 cells. This activity was further confirmed by FACS using Annexin-V-FITC and Propidium Iodide (PI) labeling. Molecular docking studies performed on 6h and 6j suggested that the compounds can bind to the hinge region of ATP binding site of EGFR tyrosine kinase in a similar pose as that of the standard drug gefitinib. Conclusion: The potential anticancer activity of compounds 6h and 6j was confirmed and need further exploration in cancer cell lines of different tissue origin and signaling pathways, as well as in animal models of cancer development.

scholarly journals Underutilized Mexican Plants: Screening of Antioxidant and Antiproliferative Properties of Mexican Cactus Fruit Juices

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 368
Author(s):  
Elda M. Melchor Martínez ◽  
Luisaldo Sandate-Flores ◽  
José Rodríguez-Rodríguez ◽  
Magdalena Rostro-Alanis ◽  
Lizeth Parra-Arroyo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Liver Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
In Vitro Assays ◽  
Total Phenolic ◽  
Liver Cancer Cell ◽  
Antiproliferative Activities

Cacti fruits are known to possess antioxidant and antiproliferative activities among other health benefits. The following paper evaluated the antioxidant capacity and bioactivity of five clarified juices from different cacti fruits (Stenocereus spp., Opuntia spp. and M. geomettizans) on four cancer cell lines as well as one normal cell line. Their antioxidant compositions were measured by three different protocols. Their phenolic compositions were quantified through high performance liquid chromatography and the percentages of cell proliferation of fibroblasts as well as breast, prostate, colorectal, and liver cancer cell lines were evaluated though in vitro assays. The results were further processed by principal component analysis. The clarified juice from M. geomettizans fruit showed the highest concentration of total phenolic compounds and induced cell death in liver and colorectal cancer cells lines as well as fibroblasts. The clarified juice extracted from yellow Opuntia ficus-indica fruit displayed antioxidant activity as well as a selective cytotoxic effect on a liver cancer cell line with no toxic effect on fibroblasts. In conclusion, the work supplies evidence on the antioxidant and antiproliferative activities that cacti juices possess, presenting potential as cancer cell proliferation preventing agents.

scholarly journals Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Suleyman Vural ◽  
Alida Palmisano ◽  
William C. Reinhold ◽  
Yves Pommier ◽  
Beverly A. Teicher ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Agents ◽  
Epigenetic Factors ◽  
Expression Of Genes ◽  
Genes Encoding

Abstract Background Altered DNA methylation patterns play important roles in cancer development and progression. We examined whether expression levels of genes directly or indirectly involved in DNA methylation and demethylation may be associated with response of cancer cell lines to chemotherapy treatment with a variety of antitumor agents. Results We analyzed 72 genes encoding epigenetic factors directly or indirectly involved in DNA methylation and demethylation processes. We examined association of their pretreatment expression levels with methylation beta-values of individual DNA methylation probes, DNA methylation averaged within gene regions, and average epigenome-wide methylation levels. We analyzed data from 645 cancer cell lines and 23 cancer types from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer datasets. We observed numerous correlations between expression of genes encoding epigenetic factors and response to chemotherapeutic agents. Expression of genes encoding a variety of epigenetic factors, including KDM2B, DNMT1, EHMT2, SETDB1, EZH2, APOBEC3G, and other genes, was correlated with response to multiple agents. DNA methylation of numerous target probes and gene regions was associated with expression of multiple genes encoding epigenetic factors, underscoring complex regulation of epigenome methylation by multiple intersecting molecular pathways. The genes whose expression was associated with methylation of multiple epigenome targets encode DNA methyltransferases, TET DNA methylcytosine dioxygenases, the methylated DNA-binding protein ZBTB38, KDM2B, SETDB1, and other molecular factors which are involved in diverse epigenetic processes affecting DNA methylation. While baseline DNA methylation of numerous epigenome targets was correlated with cell line response to antitumor agents, the complex relationships between the overlapping effects of each epigenetic factor on methylation of specific targets and the importance of such influences in tumor response to individual agents require further investigation. Conclusions Expression of multiple genes encoding epigenetic factors is associated with drug response and with DNA methylation of numerous epigenome targets that may affect response to therapeutic agents. Our findings suggest complex and interconnected pathways regulating DNA methylation in the epigenome, which may both directly and indirectly affect response to chemotherapy.

scholarly journals The application of CRISPR/Cas9 system in cervical carcinogenesis

2021 ◽  
Author(s):  
Chun Gao ◽  
Ping Wu ◽  
Lan Yu ◽  
Liting Liu ◽  
Hong Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Transgenic Mice ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Precancerous Lesions ◽  
Cancer Cell Lines ◽  
Cervical Carcinogenesis ◽  
Cervical Precancerous Lesions

AbstractIntegration of high-risk HPV genomes into cellular chromatin has been confirmed to promote cervical carcinogenesis, with HPV16 being the most prevalent high-risk type. Herein, we evaluated the therapeutic effect of the CRISPR/Cas9 system in cervical carcinogenesis, especially for cervical precancerous lesions. In cervical cancer/pre-cancer cell lines, we transfected the HPV16 E7 targeted CRISPR/Cas9, TALEN, ZFN plasmids, respectively. Compared to previous established ZFN and TALEN systems, CRISPR/Cas9 has shown comparable efficiency and specificity in inhibiting cell growth and colony formation and inducing apoptosis in cervical cancer/pre-cancer cell lines, which seemed to be more pronounced in the S12 cell line derived from the low-grade cervical lesion. Furthermore, in xenograft formation assays, CRISPR/Cas9 inhibited tumor formation of the S12 cell line in vivo and affected the corresponding protein expression. In the K14-HPV16 transgenic mice model of HPV-driven spontaneous cervical carcinogenesis, cervical application of CRISPR/Cas9 treatment caused mutations of the E7 gene and restored the expression of RB, E2F1, and CDK2, thereby reversing the cervical carcinogenesis phenotype. In this study, we have demonstrated that CRISPR/Cas9 targeting HPV16 E7 could effectively revert the HPV-related cervical carcinogenesis in vitro, as well as in K14-HPV16 transgenic mice, which has shown great potential in clinical treatment for cervical precancerous lesions.

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