In vitro inhibitory effects of polymer-linked methotrexate derivatives on tetrahydrofolate dehydrogenase and murine L5178Y cells.
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.
D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000494:pharmacology; D002478:Cells, Cultured; D005493:Folic Acid Antagonists; D007942:Leukemia, Experimental / Q000188:drug therapy*; D046911:Macromolecular Substances / Q000494:pharmacology; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D011094:Polyethyleneimine / Q000494:pharmacology; D011107:Polylysine / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology*; D011713:Pyran Copolymer / Q000494:pharmacology
D005493:Folic Acid Antagonists; D046911:Macromolecular Substances; D011108:Polymers; D011107:Polylysine; D011713:Pyran Copolymer; D011094:Polyethyleneimine; D002266:Carboxymethylcellulose Sodium; D008727:Methotrexate