Investigation of New Phenothiazine and Carbazole Derivatives as Potential Inhibitors of Human Farnesyltransferase

Title:Investigation of New Phenothiazine and Carbazole Derivatives as Potential Inhibitors of Human Farnesyltransferase

Volume: 12 Issue: 2

Author(s): Gina-Mirabela Dumitriu, Alina Ghinet, Dalila Belei, Benoit Rigo, Philippe Gautret, Joelle Dubois and Elena Bicu

Affiliation:

Keywords: Anticancer agent, carbazole, disulfide, farnesyltransferase, phenothiazine.

Abstract: A new series of phenothiazine and carbazole derivatives was synthesized and evaluated for their biological activity on human protein farnesyltransferase. The farnesyltransferase assays revealed that carbazole 4f was the best farnesyltransferase inhibitor in the current study (IC₅₀ (human FTase) = 35.0 µM), providing that the presence of the carbazole unit is important in this family of compounds. Moreover, unexpected disulfide analogues were observed during coupling reactions of activated esters 12 and 13 with aminoethanethiol and mercaptoethanol, respectively. These dimers deserve further chemical and biological investigation in order to develop new chemical entities for anticancer research.

Cite this article as:

Dumitriu Gina-Mirabela, Ghinet Alina, Belei Dalila, Rigo Benoit, Gautret Philippe, Dubois Joelle and Bicu Elena, Investigation of New Phenothiazine and Carbazole Derivatives as Potential Inhibitors of Human Farnesyltransferase, Letters in Drug Design & Discovery 2015; 12 (2) . https://dx.doi.org/10.2174/1570180811666140909010435