The Disulfide Analogues of Isophosphoramide Mustard for Anticancer Therapy
Novel disulfide analogues of isophosphoramide mustard (iPAM) were designed and synthesised. All compounds
were hydrolytically stable and underwent reduction by L-glutathione with different kinetic parameters. Based on
the HPLC-MS analysis a mechanism of activation by glutathione obtained disulfide analogues of iPAM was proposed.
The compounds were tested for cytotoxic activity against human promyelocytic leukaemia HL-60, human lymphoblastic
leukaemia MOLT-4, human lymphoblastic leukaemia CCRF/CEM, human bladder cancer HCV29T, murine melanoma
B16-F0 and murine fibroblasts Balb3T3 cell lines. The most promising anticancer activity was exhibited by compound 4,
which proved to be more active than the reference cisplatin against all cancer cell lines.
Keywords: Anticancer activity, disulfide, glutathione, isophosphoramide mustard.
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