Dual Anti-cancer and Anti-Itch Activity of PD176252 Analogues: Design, Synthesis and Biological Evaluation

2019 ◽  
Vol 19 (8) ◽  
pp. 992-1001 ◽  
Author(s):  
Ming-Jun Yu ◽  
Sen Yao ◽  
Ting-Ting Li ◽  
Rui Yang ◽  
Ri-Sheng Yao
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Normal Lung ◽  
Cancer Drug ◽  
Normal Cells ◽  
Anti Cancer ◽  
Grpr Antagonist ◽  
Cancer Activity

Background: Cancer patients treated with targeted anti-cancer drug suffer from itch or pruritus. Itch or pruritus is an unpleasant sensation that brings about a negative impact on quality of life, and serious itch may lead to dose reduction and even discontinuation. Gastrin releasing peptide receptor (GRPR) plays a critical role in itch, inflammation and cancer, and GRPR antagonist has obvious effect on cancer, inflammation and itch. The aim of this paper is to develop a new agent with anti-cancer and anti-itch activity. Methods: A series of GRPR antagonist PD176252 analogues (3a-3l) were designed and synthesized. Both anticancer and anti-itch activities were evaluated. Anti-cancer activity was evaluated in three human cancer cell lines in vitro, the anti-itch activity in evaluated with Kunming mice by intrathecal injection of chloroquine phosphate as a modeling medium. And the cytotoxicity on normal cells was evaluated. Results: Of the tested compounds, compound 3i showed potently anti-cancer activity to all cancer cell lines tested with IC50 values of 10.5µM (lung), 11.6µM (breast) and 12.8µM (liver) respectively and it also showed significant inhibition of the scratching behavior. Comparing with PD17625, compound 3i and 3g gave better inhibition activities against all cancer cell lines, compound 3b, 3c and 3i showed better anti-itch activity. The compound 3i is safe for normal breast and liver normal cells, but it has high cytotoxicity on normal lung cell. Conclusion: The synthesized compounds have dual anti-cancer and anti-itch activity, so the development of drug with dual anti-tumor and anti-itch property is possible.

Design, Synthesis and Biological Evaluation of 4, 6-Coumarin Derivatives as Anti-Cancer and Apoptosis-Inducing Agents

2021 ◽  
Vol 21 ◽  
Author(s):  
Guoyi Yan ◽  
Jiang Luo ◽  
Xuan Han ◽  
Wenjuan Zhang ◽  
Chunlan Pu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Coumarin Derivatives ◽  
In Silico Admet ◽  
Anti Cancer ◽  
Synthesis And Biological Evaluation

BACKGROUND: : Coumarin structures were widely employed in anti-cancer drug design. Herein we focused on the modifications of C4 and C6 positions on coumarin scaffold to get novel anti-cancer agents. OBJECTIVE: The objective of the current work was the synthesis and biological evaluation of a series of 4, 6-coumarin derivatives to get novel anticancer agents. METHODS: Thirty-seven coumarin derivatives were designed and synthesized, the antiproliferative activity of the compounds were evaluated against human cancer cell lines and non-cancerous cells by MTT assay. The bioactivities and underling mechanisms of active molecules were studied and the ADMET characters were predicted. RESULTS: Among the compounds, 4-phydroxy phenol-6-pinacol borane coumarin (25) exhibited a promising anti-cancer activity to cancer cell lines in dose-dependent manner and the toxicity to normal cells was low. The mechanism of action was observed through inducing G2/M phase arrest and apoptosis which was further confirmed via western blot. In silico ADMET prediction revealed that compound 25 is a drug-like small molecule with a favorable safety profile. CONCLUSION: The findings in this work may give vital information for further development of 6-pinacol borane coumarin derivatives as novel anti-cancer agents.

scholarly journals Theophylline exhibits anti-cancer activity via suppressing SRSF3 in cervical and breast cancer cell lines

Oncotarget ◽  
2017 ◽  
Vol 8 (60) ◽  
pp. 101461-101474 ◽  
Author(s):  
Yung-Lung Chang ◽  
Yu-Juei Hsu ◽  
Ying Chen ◽  
Yi-Wen Wang ◽  
Shih-Ming Huang
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Anti Cancer ◽  
Cancer Activity

scholarly journals 8-Hydroxycudraxanthone G Suppresses IL-8 Production in SP-C1 Tongue Cancer Cells

2014 ◽  
Vol 9 (1) ◽  
pp. 1934578X1400900
Author(s):  
Arlette S. Setiawan ◽  
Roosje R. Oewen ◽  
Supriatno ◽  
Willyanti Soewondo ◽  
Sidik ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Therapeutic Intervention ◽  
Tongue Cancer ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Garcinia Mangostana ◽  
Anti Cancer ◽  
Cancer Activity

Production of IL-8 primarily promotes angiogenic responses in cancer cells, which lead to favorable disease progression. Suppressing this production may, therefore, be a significant therapeutic intervention in targeting tumor angiogenesis. This study aimed to evaluate the reduction effects of xanthones in cancer cell lines. Nine known prenylated xanthones (1–9), isolated from the pericarp of Garcinia mangostana Linn (GML), were tested for their ability to suppress IL-8 (interleukin-8) of the SP-C1 (Supri's Clone 1) tongue cancer cell line. Of these compounds, 8-hydroxycudraxanthone-G (4) suppressed IL-8 within 48 hours. This is the first report of 8-hydroxycudraxanthone G suppressing the production of IL-8 (45% at 15.7 μg/mL in 48 hours). These results suggest that the prolonged suppression of IL-8 production by cancer cell lines is concerned in the anti-cancer activity of 8-hydroxycudraxanthone.

QSAR Study of the Anti-Cancer Activity of 38 Compounds in Different Cancer Cell Lines Based on Gene Expression Programming

2013 ◽  
Vol 850-851 ◽  
pp. 1291-1294
Author(s):  
Xiu Rui Han ◽  
Xian Chao Li ◽  
Hong Zong Si ◽  
Cui Zhu Ge ◽  
Hua Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gene Expression Programming ◽  
Test Group ◽  
Qsar Model ◽  
Cancer Cell Lines ◽  
Qsar Study ◽  
Anti Cancer ◽  
Cancer Activity

Using the GEP,the QSAR model for anti-cancer activity of 38 compounds in 5 cancer cell lines was establish. These compounds are a novel class of anticarcinogen named tricyclic 5:7:5-fused diimidazo [4, 5-d:4, 5-f ][1, diazepines. The carcinoma cell lines involved in this research are A549 lung cancer, MCF-7 breast cancer, MDA-MB-231 breast cancer, OVCAR-3 ovarian cancer and PC-3 prostate cancer. Accuracies of these models in training group and test group are over 90%, showing perfect predictive ability. This QSAR model will be great valuable in providing guidance for future designing and synthesizing of anticancer drugs.

scholarly journals Lanatoside C Induces G2/M Cell Cycle Arrest and Suppresses Cancer Cell Growth by Attenuating MAPK, Wnt, JAK-STAT, and PI3K/AKT/mTOR Signaling Pathways

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 792 ◽  
Author(s):  
Dhanasekhar Reddy ◽  
Ranjith Kumavath ◽  
Preetam Ghosh ◽  
Debmalya Barh
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Mtor Signaling ◽  
Anti Cancer ◽  
Cancer Activity ◽  
Lanatoside C

Cardiac glycosides (CGs) are a diverse family of naturally derived compounds having a steroid and glycone moiety in their structures. CG molecules inhibit the α-subunit of ubiquitous transmembrane protein Na+/K+-ATPase and are clinically approved for the treatment of cardiovascular diseases. Recently, the CGs were found to exhibit selective cytotoxic effects against cancer cells, raising interest in their use as anti-cancer molecules. In this current study, we explored the underlying mechanism responsible for the anti-cancer activity of Lanatoside C against breast (MCF-7), lung (A549), and liver (HepG2) cancer cell lines. Using Real-time PCR, western blot, and immunofluorescence studies, we observed that (i) Lanatoside C inhibited cell proliferation and induced apoptosis in cell-specific and dose-dependent manner only in cancer cell lines; (ii) Lanatoside C exerts its anti-cancer activity by arresting the G2/M phase of cell cycle by blocking MAPK/Wnt/PAM signaling pathways; (iii) it induces apoptosis by inducing DNA damage and inhibiting PI3K/AKT/mTOR signaling pathways; and finally, (iv) molecular docking analysis shows significant evidence on the binding sites of Lanatoside C with various key signaling proteins ranging from cell survival to cell death. Our studies provide a novel molecular insight of anti-cancer activities of Lanatoside C in human cancer cells.

Anti-cancer activity of NVP-TAE226, a potent dual FAK/IGF-IR kinase inhibitor, against pancreatic carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13162-13162 ◽  
Author(s):  
S. Hatakeyama ◽  
D. Tomioka ◽  
E. Kawahara ◽  
N. Matsuura ◽  
K. Masuya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pancreatic Carcinoma ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Normal Cells ◽  
P Glycoprotein ◽  
Anti Cancer ◽  
Cancer Activity

13162 Background: Focal adhesion kinase (FAK) is a non-receptor cytoplasmic tyrosine kinase that regulates multiple cell functions. Elevated expression levels of FAK have been detected in various tumor samples and are closely correlated with invasive potential. Activation of integrins and the growth factor receptors result in FAK autophosphorylation at Y397 and the presentation of suitable binding sites for proteins containing either SH2 or phosphotyrosine binding domains. Recent evidences suggest that FAK plays important roles in cancer cell proliferation and survival. IGF-IR function is required for tumor cell survival, but dispensable for survival of normal cells. Therefore, a dual inhibitor of both kinases may selectively block the growth, migration, and survival of FAK- and IGF-IR- expressing tumor cells compared to proliferating and migrating normal cells. Methods: In this study, anti-cancer activity of NVP-TAE226 that is identified as a potent and selective FAK inhibitor was evaluated in cancer cell lines panel and MIA PaCa-2 pancreatic carcinoma in vivo model. Results: Mean GI50 value of NVP-TAE226 against 37 cancer cell lines was 0.76 μmole/L. Inhibition of cancer cell proliferation was not affected by expression of P-glycoprotein, suggesting that NVP-TAE226 is not served as a substrate of P-glycoprotein. Oral administration of NVP-TAE226 efficiently inhibited MIA PaCa-2 human pancreatic tumor growth at all doses tested. Tumor stasis was observed at a dose of 30 mg/kg, qd for 7×/week and tumor regression was observed at a dose of 100 mg/kg, qd for 5×/week. All animals tolerated NVP-TAE226 treatment up to 100 mg/kg, 5×/wk, qd, po for 2 weeks with no body weight loss. Inhibition of downstream signaling such as phosphorylation of Akt at Serine473 was accompanied by inhibition of FAK phosphorylation in human pancreatic carcinoma cell lines. Conclusions: NVP-TAE226 is a novel class of selective and small molecule kinase inhibitors with a potent in vivo activity and potential therapeutic application. No significant financial relationships to disclose.

Anti-cancer activity of pegylated liposomal trans-anethole on breast cancer cell lines MCF-7 and T47D

2015 ◽  
Vol 37 (7) ◽  
pp. 1355-1359 ◽  
Author(s):  
Shahedeh Shahbazian ◽  
Azim Akbarzadeh ◽  
Sepideh Torabi ◽  
Mansour Omidi
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Anti Cancer ◽  
Cancer Activity ◽  
Mcf 7
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