Isophosphoramide mustard analogues as prodrugs for anti-cancer gene-directed enzyme-prodrug therapy (GDEPT).

• Authors: Konrad Misiura , Daria Szymanowicz , Halina Kuśnierczyk , Joanna Wietrzyk , Adam Opolski
• Languages of publication: EN

Abstracts

EN

Two types of prodrugs, benzyl analogues of isophosphoramide mustard (iPAM), activated by cytochrome P450, and acylthioethyl analogues, activated by esterases, were designed. In contrast to iPAM that hydrolyse rapidly, the examined compounds are stable in phosphate-buffered saline and Tris buffer. Benzyl analogues of iPAM are poor substrates for cytochrome P450, are not cytotoxic and posses no antitumour activity. Acylthioethyl analogues of iPAM are good substrates for pig liver esterase, are cytotoxic and exert antitumour activity against L1210 leukaemia in mice. The observed correlation for iPAM analogues between their susceptibility to hydrolysis and cytotoxicity and antitumour activity suggests possible application of these compounds as the prodrugs in gene-directed enzyme-prodrug therapy.

Keywords

EN

prodrugs; GDEPT; ifosfamide; isophosphoramide mustard; antitumour treatment

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2002
• Volume: 49
• Issue: 1
• Pages: 169-176

Dates

published

2002

received

2001-09-10

revised

2002-01-31

accepted

2002-02-14

Contributors

author

Konrad Misiura

• Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland

author

Daria Szymanowicz

• Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland

author

Halina Kuśnierczyk

• Department of Tumour Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland

author

Joanna Wietrzyk

• Department of Tumour Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland

author

Adam Opolski

• Department of Tumour Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland

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