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In vitro inhibitory effects of polymer-linked methotrexate derivatives on tetrahydrofolate dehydrogenase and murine L5178Y cells

Fung, W.P.; Przybylski, M.; Ringsdorf, H.; Zaharko, D.S.

Journal of the National Cancer Institute 62(5): 1261-1264

1979

ISSN/ISBN: 0027-8874
PMID: 286102
Document Number: 154192
In vitro studies were made on four synthetic polymeric derivatives of the antitumor agent methotrexate (MTX): 1) divinylether-maleic anhydride-MTX (DIVEMA-MTX), 2) poly-L-lysine-MTX (PL-MTX), 3) polyethyleneimine-MTX (PEI-MTX), and 4) carboxymethyl cellulose-MTX (CMC-MTX). They were tested for their ability to inhibit tetrahydrofolate dehydrogenase (dihydrofolate reductase). Their growth inhibition of murine L5178Y leukemia cells was also studied. 1wo of these polymers, DIVEMA-MTX and PEI-MTX, had similar or only slightly reduced activity compared to equivalent concentrations of MTX, whereas PL-MTX and CMC-MTX had significantly higher (1--3 logs) minimal inhibitory concentrations.

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