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 Oct 30;18(11):13385-97. doi: 10.3390/molecules181113385.

Abstract

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 9-11) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Viruses / drug effects
  • HeLa Cells
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology*
  • RNA Viruses / drug effects
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Antiviral Agents
  • Imidazoles
  • imidazole