Next Article in Journal
A Piston-Rotaxane with Two Potential Stripes: Force Transitions and Yield Stresses
Previous Article in Journal
Synthesis, Characterization, X-ray Structure and Biological Activities of C-5-Bromo-2-hydroxyphenylcalix[4]-2-methyl resorcinarene
Molecules 2013, 18(11), 13385-13397; doi:10.3390/molecules181113385

The Novel [4,5-e][1,3]Diazepine-4,8-dione and Acyclic Carbamoyl Imino-Ureido Derivatives of Imidazole: Synthesis, Anti-Viral and Anti-Tumor Activity Evaluations

, 1
, 1
, 2,3
, 2,3
, 4
, 5
, 5
, 5
 and 1,*
1 Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 20, Zagreb HR-10000, Croatia 2 Slovenian NMR Centre, National Institute of Chemistry, Hajdrihova 19, P. O. B. 660, Ljubljana SI-1001, Slovenia 3 EN-FIST Centre of Excellence, Dunajska 156, Ljubljana SI-1001, Slovenia 4 Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium 5 Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, Rijeka 51000, Croatia
* Author to whom correspondence should be addressed.
Received: 29 August 2013 / Revised: 5 October 2013 / Accepted: 17 October 2013 / Published: 30 October 2013
Download PDF [317 KB, uploaded 18 June 2014]


In the present paper, we report on the synthesis, and in vitro antiviral and cytostatic activities of a series of novel imidazole[4,5-e][1,3]diazepine-4,8-dione (compounds 911) and acyclic carbamoyl imino-ureido imidazole (compounds 12 and 13) derivatives. These new type of chemical entities showed no significant activity on the broad spectrum of DNA and RNA viruses. Results of antiproliferative assays performed on a panel of selected human tumor cell lines revealed that only compounds 1 and 5 showed moderate and selective cytostatic effect against HeLa cells (IC50 = 24 and 32 µM) with no concomitant cytotoxic effects on human normal fibroblasts (BJ). Importantly, an imidazole derivative containing a pyrrolidine moiety linked via an ethylenic spacer (3) showed a selective cytostatic effect toward cervical carcinoma (HeLa) cells (IC50 = 9.5 µM) with no apparent cytotoxicity on human normal fibroblasts (BJ). This compound can be therefore considered as a potential anti-tumor lead compound for further synthetic structure optimization.
Keywords: imidazole; [4,5-e][1,3]diazepine; anti-RSV; anti-tumor imidazole; [4,5-e][1,3]diazepine; anti-RSV; anti-tumor
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.

Share & Cite This Article

Export to BibTeX |

MDPI and ACS Style

Wittine, K.; Poljak, K.; Kovač, M.; Makuc, D.; Plavec, J.; Balzarini, J.; Martinović, T.; Pavelić, S.K.; Pavelić, K.; Mintas, M. The Novel [4,5-e][1,3]Diazepine-4,8-dione and Acyclic Carbamoyl Imino-Ureido Derivatives of Imidazole: Synthesis, Anti-Viral and Anti-Tumor Activity Evaluations. Molecules 2013, 18, 13385-13397.

View more citation formats

Related Articles

Article Metrics


Citing Articles

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