A new strategy for the modification of cyclophosphamide was carried out and three series of new cyclophosphamide piperazinium salts 10,11 and 13 were prepared.These compounds,based on compound 9i scaffold,were evaluat...A new strategy for the modification of cyclophosphamide was carried out and three series of new cyclophosphamide piperazinium salts 10,11 and 13 were prepared.These compounds,based on compound 9i scaffold,were evaluated for their in vivo anticancer activities against hepatocyte sarcoma 22 （H 22）.The structure-activity relationship study reveals that 1） the conformation and the substituent at N-3 of cyclophosphamide spiropiperazinium salts 10 greatly affect the activity 2） different kinds of cyclophosphamide non-spiropiperazinium derivatives 11 show different activities 3） for 1,2-benzisoxazole phosphoropiperazinium salts 13,it is possible to obtain anticancer drug candidates with suitable quaternary ammonium moiety.These results would help to further design and synthesize analogs of mustard anticancer drugs.展开更多
To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro an...To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro anticancer activities were evaluated. The four peptide cycloacetal derivatives did not showed any activities, which demonstrated that this kind of cycloacetal derivatives might be suitable as prodrugs. The two peptide heterocycle compounds were found to show obvious activities at both enzyme and cell levels. These results provide us a new clue for the modification of peptide aldehyde proteasome inhibitors.展开更多
基金Foundation items:National Nature Science Foundation of China (Grant No. 20472008)the Major State Basic Research Development Program (Grant No. 2004CB719900)
文摘A new strategy for the modification of cyclophosphamide was carried out and three series of new cyclophosphamide piperazinium salts 10,11 and 13 were prepared.These compounds,based on compound 9i scaffold,were evaluated for their in vivo anticancer activities against hepatocyte sarcoma 22 （H 22）.The structure-activity relationship study reveals that 1） the conformation and the substituent at N-3 of cyclophosphamide spiropiperazinium salts 10 greatly affect the activity 2） different kinds of cyclophosphamide non-spiropiperazinium derivatives 11 show different activities 3） for 1,2-benzisoxazole phosphoropiperazinium salts 13,it is possible to obtain anticancer drug candidates with suitable quaternary ammonium moiety.These results would help to further design and synthesize analogs of mustard anticancer drugs.
基金National Natural Science Foundation of China (Grant No.30772626)
文摘To improve the stability of peptide aldehyde proteasome inhibitors, four peptide cycloacetal derivatives and two peptide heterocycle compounds were designed and synthesized. Their proteasome inhibition and in vitro anticancer activities were evaluated. The four peptide cycloacetal derivatives did not showed any activities, which demonstrated that this kind of cycloacetal derivatives might be suitable as prodrugs. The two peptide heterocycle compounds were found to show obvious activities at both enzyme and cell levels. These results provide us a new clue for the modification of peptide aldehyde proteasome inhibitors.
