Development of potential anti‐cancer agents: Diazenes and derivatives

Abstract

AbstractThe call for the discovery of more effective agents to treat cancer has become urgent. Recently, we have synthesized new compounds: diazenes. So far, we have demonstrated that several of them inhibited the growth of tumor cells, but their solubility and biological activity were relatively low. Therefore, new compounds have been synthesized to improve their solubility and biological efficacy. In the present study, we screened cytotoxicity of 26 new diazenes and their derivatives on human cervical carcinoma HeLa cells. The most active compound was tested also on human laryngeal carcinoma, breast adenocarcinoma, and glioblastoma cells, as well as on two drug‐resistant sublines derived from cervical and laryngeal carcinoma cells. Cytotoxicity of new compounds was determined using a colorimetric MTT assay. Results show that diazene SB‐681 was the most efficient one, reducing significantly survival of HeLa cells, with IC50 value of 16.3 μM. This compound applied in low doses inhibited also the growth of other cell lines tested, among which were two drug‐resistant cell lines. The observed activity could be explained by the influence of groups attached to the diazene functionality, namely 2‐chloroethylaminocarbonyl moiety and pentafluorophenyl moiety attached to the diazene nitrogen‐nitrogen double bond. Our data indicate that SB‐681 is a promising leading compound in the development of a novel class of antineoplastic agents. Drug Dev. Res. 61:95–100, 2004. © 2004 Wiley‐Liss, Inc.