Synthesis and Antitumor Activity Evaluation of a Novel Combi-nitrosourea Prodrug: BGCNU.

ABSTRACT: Chloroethylnitrosoureas (CENUs) are an important type of alkylating agent employed in the clinical treatment of cancer. However, the anticancer efficacy of CENUs is greatly decreased by a DNA repairing enzyme, O⁶-alkylguanine-DNA alkyltransferase (AGT), by preventing the formation of interstrand cross-links (ICLs). In this study, a combi-nitrosourea prodrug, namely, N-(2-chloroethyl)-N'-2-(O⁶-benzyl-9-guanine)ethyl-N-nitrosourea (BGCNU), which possesses an O⁶-benzylguanine (O⁶-BG) derivative and CENU pharmacophores simultaneously, was synthesized and evaluated for its ability to induce ICLs. The target compound is markedly more cytotoxic in human glioma cells than the clinically used CENU chemotherapies ACNU, BCNU, and their

SUBMITTER: Wang Y 

PROVIDER: S-EPMC5304294 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature