Isophosphoramide mustard analogues as prodrugs for anticancer gene-directed enzyme-prodrug therapy [GDEPT]

• Autorzy: Misiura K. , Szymanowicz D. , Kusnierczyk H. , Wietrzyk J. , Opolski A.
• Języki publikacji: EN

Abstrakty

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.

Słowa kluczowe

EN

isophosphoramide mustard; antitumour treatment; prodrug; therapy; cytochrome P450; anticancer gene

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2002
• Tom: 49
• Numer: 1
• Opis fizyczny: p.169-176

Twórcy

autor

Misiura K.

• Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland

autor

Szymanowicz D.

autor

Kusnierczyk H.

autor

Wietrzyk J.

autor

Opolski A.

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