Synthesis, anticancer activity, toxicity evaluation and molecular docking studies of novel phenylaminopyrimidine-(thio)urea hybrids as potential kinase inhibitors.

2019-02-01
Ture, Asli
Kahraman, Deniz Cansen
Atalay, Rengül
Helvacioglu, Sinem
Charehsaz, Mohammad
KÜÇÜKGÜZEL, İLKAY
Show full item record
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
180
views
0
downloads
Thirty-two novel urea/thiourea compounds as potential kinase inhibitor were designed, synthesized and evaluated for their cytotoxic activity on breast (MCF7), colon (HCT116) and liver (Huh7) cancer cell lines. Compounds 10, 19 and 30 possessing anticancer activity with IC50 values of 0.9, 0.8 and 1.6 mu M respectively on Huh7 cells were selected for further studies. These hit compounds were tested against liver carcinoma panel. Real time cell electronic sensing assay was used to evaluate the effects of the compounds 10, 19 and 30 on the growth pattern of liver cancer cells. Apoptotic cell death and cell cycle analysis upon treatment of liver carcinoma cells with hit compounds were determined. A significant apoptotic cell death was detected upon treatment of Huh7 and Mahlavu cells with compound 30 after 48 h of treatment. Additionally, compound 10 caused cell cycle arrest at G0/G1 phase. Mutagenicity of hit compounds was evaluated. Assertively, these compounds were not found to be mutagenic on Salmonella typhimurium strains TA98 and TA100. To understand the binding modes of the synthesized compounds, molecular docking studies were performed using the crystal data of VEGFR and Src-kinase enzymes in correlation with anticancer activities.
Phenylaminopyrimidines, Ureas, Thioureas, Cancer, Molecular docking, Src-kinase, VEGFR
https://hdl.handle.net/11511/32513
Computational biology and chemistry
Graduate School of Informatics, Article

Suggestions

Synthesis and cellular bioactivities of novel isoxazole derivatives incorporating an arylpiperazine moiety as anticancer agents.
ÇALIŞKAN, BURCU; Nalbat, Esra; Ibis, Kubra; Guzelcan, Ece Akhan; Atalay, Rengül; BANOĞLU, ERDEN (2018-12-01)
In our endeavour towards the development of effective anticancer therapeutics, a novel series of isoxazole-piperazine hybrids were synthesized and evaluated for their cytotoxic activities against human liver (Huh7 and Mahlavu) and breast (MCF-7) cancer cell lines. Within series, compounds 51-o showed the most potent cytotoxicity on all cell lines with IC50 values in the range of 0.3-3.7 mu M. To explore the mechanistic aspects fundamental to the observed activity, further biological studies with 5m and 5o i...
Synthesis of novel 6-substituted amino-9-(beta-D-ribofuranosyl)purine analogs and their bioactivities on human epithelial cancer cells
TUNÇBİLEK, MERAL; Kucukdumlu, Asligul; Guven, Ebru Bilget; Altiparmak, Duygu; Atalay, Rengül (2018-02-01)
New nucleoside derivatives with nitrogen substitution at the C-6 position were prepared and screened initially for their in vitro anticancer bioactivity against human epithelial cancer cells (liver Huh7, colon HCT116, breast MCF7) by the NCI-sulforhodamine B assay. N-6-(4-trifluoromethylphenyl) piperazine analog (27) exhibited promising cytotoxic activity. The compound 27 was more cytotoxic (IC50 = 1-4 mu M) than 5-FU, fludarabine on Huh7, HCT116 and MCF7 cell lines. The most potent nucleosides (11, 13, 16,...
Synthesis of Some Substituted 6-Phenyl Purine Analogues and Their Biological Evaluation as Cytotoxic Agents
Kucukdumlu, Asligul; Tuncbilek, Meral; Guven, Ebru Bilget; Atalay, Rengül (2017-01-01)
A series of 6-(4-substituted phenyl)-9-(tetrahydropyran-2-yl) purines 3-9, 6-(4-substituted phenyl) purines 10-16, 9-((4-substituted phenyl) sulfonyl)-6-(4-substituted phenyl) purines 17-32 were prepared and screened initially for their in vitro anticancer activity against selected human cancer cells (liver Huh7, colon HCT116, breast MCF7). 6-(4-Phenoxyphenyl) purine analogues 9, 16, 30-32, had potent cytotoxic activities. The most active purine derivatives 5-9, 14, 16, 18, 28-32 were further screened for t...
Synthesis and biological evaluation of novel isoxazole-piperazine hybrids as potential anti-cancer agents with inhibitory effect on liver cancer stem cells
Ibis, Kubra; Sinoplu, Esra; ÇALIŞKAN, BURCU; Kahraman, Deniz Cansen; Cetin-Atalay, Rengul; BANOĞLU, ERDEN (2021-10-01)
In our effort for the development of novel anticancer therapeutics, a series of isoxazole-piperazine analogues were prepared, and primarily screened for their antiproliferative potential against hepatocellular carcinoma (HCC; Huh7/Mahlavu) and breast (MCF-7) cancer cells. All compounds demonstrated potent to moderate cytotoxicity on all cell lines with IC50 values in the range of 0.09-11.7 mu M. Further biological studies with 6a and 13d in HCC cells have shown that both compounds induced G1 or G2/M arrests...
Synthesis of poly (dl-lactic-co-glycolic acid) coated magnetic nanoparticles for anti-cancer drug delivery
Tansık, Gülistan; Gündüz, Ufuk; Department of Biology (2012)
One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
Citation Formats
A. Ture, D. C. Kahraman, R. Atalay, S. Helvacioglu, M. Charehsaz, and İ. KÜÇÜKGÜZEL, “Synthesis, anticancer activity, toxicity evaluation and molecular docking studies of novel phenylaminopyrimidine-(thio)urea hybrids as potential kinase inhibitors.,” Computational biology and chemistry, pp. 227–241, 2019, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/32513.
METU IIS - Integrated Information Service open@metu.edu.tr