药物化学

Z-GP Modification to CI-994, a Histone Deacetylase Inhibitor and the Application in Targeting Carcinoma Chemotherapy

Abstract

Yuanyuan Deng, Peipei Gao, Cuiping Guo, Long Wu, Jun Xu, Heru Chen and Shao-hui Cai

An adduct, namely (S)-4-acetamido-N-(2-(N-benzyloxycarbonyl- glycylprolyl)aminophenyl)benzamide (Z-GPCI- 994) has been designed and synthesized. All the evidences disclose that Z-GP-CI-994 is not the substrate of fibroblast activation protein-α (FAPα). However, the adduct is the substrate of another unknown enzyme which is ubiquitous in tumor tissue. The cytotoxicity of the adduct against HepG2, A549 and NIH3T3 cell lines is apparently decreased when compared to that of the parent compound (CI-994). Additionally, the inhibition rate of Z-GP-CI-994 on histone deacetylase is significantly lower than that of CI-994. All the results suggest preliminarily that Z-GP-CI-994 is promising to achieve enzyme-targeting delivery and to reduce systemic toxicity.