A novel class of cyclophosphamide prodrug: structure-activity relationships of cyclophosphamide piperaziniums

Abstract

Abstract: 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 (H22). 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.

Key words: Cyclophosphamide piperaziniums, Prodrug, Anticancer activity, Synthesis, DNA-binding

CLC Number:

R916.41

Supporting:

Qing Yang, Ji-Rang Zhu, Qi Sun^*, Jing-Rong Cui, Run-Tao Li, Ze-Mei Ge^* . A novel class of cyclophosphamide prodrug: structure-activity relationships of cyclophosphamide piperaziniums [J]. .

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