1217809-60-3Relevant academic research and scientific papers
A novel melphalan polymeric prodrug: Preparation and property study
Li, Dan,Lu, Bo,Huang, Zhijun,Xu, Peihu,Zheng, Hua,Yin, Yihua,Xu, Haixing,Liu, Xia,Chen, Lingyun,Lou, Yiceng,Zhang, Xueqiong,Xiong, Fuliang
, p. 928 - 935 (2014)
The clinical application of melphalan (Me), an anticancer drug for the treatment of hematologic malignancies, has been limited due to its poor water solubility, rapid elimination and lack of target specificity. To solve these problems, O,N-carboxymethyl chitosan-peptide-melphalan conjugates were synthesized and characterized. All polymeric prodrugs showed satisfactory water solubility. It was found that the molecular weight of O,N-carboxymethyl chitosan (O,N-CMCS) and the peptide spacer played a crucial role in controlling the drug content, diameter and drug release properties of O,N-carboxymethyl chitosan-peptide-melphalan conjugates. The studies of in vitro drug release and cell cytotoxicity by MTT assay revealed that, employing the polymeric conjugation strategy and using the peptides glycylglycine (Gly-Gly) as a spacer, the conjugates have good cathepsin X-sensitivity and lower toxicity and the drug release behavior improved remarkably. In conclusion, O,N-carboxymethyl chitosan-peptide-melphalan conjugates could be promising prodrugs for anticancer application.
Preparation, characterization, and in vitro efficacy of O-carboxymethyl chitosan conjugate of melphalan
Lu, Bo,Huang, Dan,Zheng, Hua,Huang, Zhijun,Xu, Peihu,Xu, Haixing,Yin, Yihua,Liu, Xia,Li, Dan,Zhang, Xueqiong
, p. 36 - 42 (2013)
A series of melphalan-O-carboxymethyl chitosan (Mel-OCM-chitosan) conjugates with different spacers were prepared and structurally characterized. All conjugates showed satisfactory water-solubility (160- 217 times of Mel solubility). In vitro drug release behaviors by both chemical and enzymatic hydrolysis were investigated. The prodrugs released Mel rapidly within papain and lysosomal enzymes of about 40-75%, while released only about 4-5% in buffer and plasma, which suggested that the conjugates have good plasma stability and the hydrolysis in both papain and lysosomes occurs mostly via enzymolysis. It was found that the spacers have important effect on the drug content, water solubility, drug release properties and cytotoxicity of Mel-OCM-chitosan conjugates. Cytotoxicity studies by MTT assay demonstrated that these conjugates had 52-70% of cytotoxicity against RPMI8226 cells in vitro as compared with free Mel, indicating the conjugates did not lose anti-cancer activity of Mel. Overall these studies indicated Mel-OCM-chitosan conjugates as potential prodrugs for cancer treatment.
Novel melphalan and chlorambucil derivatives of 2,2,6,6-tetramethyl-1- piperidinyloxy radicals: Synthesis, characterization, and biological evaluation in vitro
Zhao, Hongli,Meng, Xianjiang,Yuan, Huihui,Lan, Minbo
experimental part, p. 332 - 335 (2011/02/25)
A series of spin-labeled melphalan and chlorambucil derivatives, coupling the alkylating agents with 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) radicals, were synthesized, characterized, and their biological properties in vitro were evaluated. These com
