In Vitro Inhibitory Effects of Polymer-Linked Methotrexate Derivatives on Tetrahydrofolate Dehydrogenase and Murine L5178Y Cells.

Abstract

In vitro studies were made on four synthetic polymeric derivatives of the antitumor agent methotrexate (MTX): 1) divinylether-maleic anhydrlde-MTX (DIVEMA-MTX), 2) poly-L-lysine-MTX (PL-MTX), 3) polyethylenelmlne-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. Two 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.