Synthesis and biological evaluation of novel isoxazole-piperazine hybrids as potential anti-cancer agents with inhibitory effect on liver cancer stem cells

Date

2021-10-01

Author

Ibis, Kubra
Sinoplu, Esra
ÇALIŞKAN, BURCU
Kahraman, Deniz Cansen
Cetin-Atalay, Rengul
BANOĞLU, ERDEN

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

332
views

0
downloads

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 resulting in apoptotic cell death. Subsequent analysis of proteins involved in cell cycle progression as well as proliferation of HCC cells revealed that 6a and 13d may affect cellular survival pathways differently depending on the mutation profiles of cells (p53 and PTEN), epidermal/ mesenchymal characteristics, and activation of cell mechanisms through p53 dependent/independent pathways. Lastly, we have demonstrated the potential anti-stemness properties of these compounds in which the proportion of liver CSCs in Huh7 cells (CD133+/EpCAM+) were significantly reduced by 6a and 13d. Furthermore, both compounds caused a significant reduction in expression of stemness markers, NANOG or OCT4 proteins, in Mahlavu and Huh7 cells, as well as resulted in a decreased sphere formation capacity in Huh7 cells. Together, these novel isoxazole-piperazine derivatives may possess potential as leads for development of effective anti-cancer drugs against HCC cells with stem cell-like properties.

Subject Keywords

Cancer, LiverIsoxazole, Piperazine, Cancer stem cell

URI

https://hdl.handle.net/11511/91643

Journal

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

DOI

https://doi.org/10.1016/j.ejmech.2021.113489

Collections

Graduate School of Informatics, Article

Suggestions

OpenMETU
Core

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...
Utilization of Scytalidium thermophilum phenol oxidase in bioorganic synthesis Kaptan, Yelda; Ögel, Zümrüt Begüm; Department of Biotechnology (2004) In this study, the ultimate aim was to utilize phenol oxidases of Scytalidium thermophilum in bioorganic syntheses. For this purpose, studies were conducted towards enhancing the production of phenol oxidases by Scytalidium thermophilum, developing a suitable method for laccase activity assays, analyzing the effects of organic solvents on phenol oxidase activity and analysis of the biotransformation of a number of organic substrates by phenol oxidases of Scytalidium thermophilum. In order to enhance the pro...
Synthesis, anticancer activity, toxicity evaluation and molecular docking studies of novel phenylaminopyrimidine-(thio)urea hybrids as potential kinase inhibitors. Ture, Asli; Kahraman, Deniz Cansen; Atalay, Rengül; Helvacioglu, Sinem; Charehsaz, Mohammad; KÜÇÜKGÜZEL, İLKAY (2019-02-01) 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 ...
Examination of the coping processes of caregivers of children with cancer Demirtepe Saygılı, Dilek; Bozo Özen, Özlem; Department of Psychology (2013) The general aim of the present dissertation was to examine the coping processes of the caregivers of children with cancer. It was composed of three studies, whose aims were (1) to reveal the predictors of caregiver distress by using the Transactional Theory of Coping among the caregivers of children with cancer; (2) to identify the factors associated with caregiving process from the caregiver’s perspective qualitatively; (3) to develop and implement an intervention program. Study 1 was conducted with 105 pa...
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

K. Ibis, E. Sinoplu, B. ÇALIŞKAN, D. C. Kahraman, R. Cetin-Atalay, and E. BANOĞLU, “Synthesis and biological evaluation of novel isoxazole-piperazine hybrids as potential anti-cancer agents with inhibitory effect on liver cancer stem cells,” EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, pp. 0–0, 2021, Accessed: 00, 2021. [Online]. Available: https://hdl.handle.net/11511/91643.