Synthesis and Evaluation of A Water-Soluble Epothilone B Prodrug with Remarkably Decreased Toxicity

Background: Instability of the macrolide, high toxicity and water insolubility of epothilone B derivatives limit their application as clinical injectable drugs. For example, PEGlated epothilone B was reported to ameliorate its water solubility and stability, and cyclodextrins polymer (CDP) was also used to drug delivery of epothilones. However, ectogenic polymers may cause lots of potential adverse reactions because of incompatibility with human body. Glutathione, a water-soluble endogenous tripeptide, plays an important role in the biological systems and involves multiple cellular functions, which seems to be a preferred compound for drug delivery. Thus, this paper report here the synthesis and evaluation of glutathione-epothilone B. Keywords: Epothilone B, glutathione, prodrug, anticancer agents, low toxic, water-soluble.