Next Article in Journal
The Chemical Reactivity of Anthocyanins and Its Consequences in Food Science and Nutrition
Next Article in Special Issue
Design, Synthesis and Docking Studies of Novel Macrocyclic Pentapeptides as Anticancer Multi-Targeted Kinase Inhibitors
Previous Article in Journal
O-GlcNAc Code’ Mediated Biological Functions of Downstream Proteins
Previous Article in Special Issue
Identification by Molecular Docking of Homoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(8), 1969; https://doi.org/10.3390/molecules23081969

Synthesis, Molecular Docking and Anticancer Activity of Diflunisal Derivatives as Cyclooxygenase Enzyme Inhibitors

1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cumhuriyet University, Sivas 58140, Turkey
2
Department of Bioinformatics and Genetic, Faculty of Engineering and Natural Sciences, Kadir Has University, Istanbul 34083, Turkey
3
Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Kayışdağı, Istanbul 34755, Turkey
4
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, Istanbul 34668, Turkey
*
Author to whom correspondence should be addressed.
Received: 2 July 2018 / Revised: 23 July 2018 / Accepted: 31 July 2018 / Published: 6 August 2018
Full-Text   |   PDF [2680 KB, uploaded 6 August 2018]   |  

Abstract

Cyclooxygenase enzymes play a vital role in inflammatory pathways in the human body. Apart from their relation with inflammation, the additional involvement of COX-2 enzyme with cancer activity was recently discovered. In some cancer types the level of COX-2 enzyme is increased indicating that this enzyme could be a suitable target for cancer therapy. Based on these findings, we have synthesized some new diflunisal thiosemicarbazides and 1,2,4-triazoles and tested them against androgen-independent prostate adenocarcinoma (PC-3), colon carcinoma (HCT-116), human breast cancer (T47D), breast carcinoma (MCF7) and human embryonic kidney (HEK-293) cell lines. Specifically, the diflunisal and thiosemicarbazide functionality are combined during the synthesis of original compounds anticipating a potency enhancement. Compounds 6, 10, 15 and 16 did not show cytotoxic effects for the HEK293 cell line. Among them, compounds 15 and 16 demonstrated anticancer activity for the breast cancer cell line T47D, whereas compounds 6 and 10 which are thiosemicarbazide derivatives displayed anti-tumourigenic activity against the PC-3 cell line, consistent with the literature. However, no activity was observed for the HCT-116 cancer cell line with the tested thiosemicarbazide derivatives. Only compound 16 displayed activity against the HCT-116 cell line. Therefore, it was speculated that the diflunisal and thiosemicarbazide functionalities potentiate anticancer activity on prostate cancer and the thiosemicarbazide functionality decreases the anticancer activity of diflunisal on colon cancer cell lines. In order to gain insight into the anticancer activity and COX-2 inhibition, molecular docking studies were carried out for COX-1 and COX-2 enzymes utilizing the newly synthesized compounds 15, and 16. Both 15 and 16 showed high selectivity and affinity toward COX-2 isozyme over COX-1, which is in agreement with the experimental results. View Full-Text
Keywords: diflunisal; thiosemicarbazide; 1,2,4-triazole-3-thione; anticancer; COX-2; docking diflunisal; thiosemicarbazide; 1,2,4-triazole-3-thione; anticancer; COX-2; docking
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Coşkun, G.P.; Djikic, T.; Hayal, T.B.; Türkel, N.; Yelekçi, K.; Şahin, F.; Küçükgüzel, Ş.G. Synthesis, Molecular Docking and Anticancer Activity of Diflunisal Derivatives as Cyclooxygenase Enzyme Inhibitors. Molecules 2018, 23, 1969.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top