title: Antitumor characteristics of the conjugate of N4-(4-carboxybutyryl)-ara-C with ethylenediamine-introduced dextran and its resistance to cytidine deaminase.
abstract: By oxidation of dextran, and reduction of the Schiff bases formed by reaction of the oxidised dextran with diaminoalkanes, several diaminoalkane-introduced dextrans were prepared and evaluated as drug carriers. Conjugates between N4-(4-carboxyburyryl)-1-beta-D-arabinofuranosylcytosine (glu-ara-C) and such drug carriers were prepared, and selected conjugates were tested in vivo, and investigated for inhibitory effects on cytidine deaminase. Ethylenediamine-introduced dextran prepared under 10% oxidation conditions was found to be most useful as a drug carrier from its chemical characteristics and toxicity evaluation in BDF1 mice. The conjugate obtained from glu-ara-C and ethylenediamine-introduced dextran 2000 showed high antitumor activity, significant at the relatively low dose of 100 mg equivalent ara-C/kg, in BDF1 mice bearing L1210 leukemia cells. Glu-ara-C and the conjugate were unaffected by cytidine deaminase under conditions in which 1-beta-D-arabinofuranosylcytosine was degraded rapidly to 1-beta-D-arabinofuranosyluracil.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Onishi
authors.forename: P
authors.initials: P
authors.lastname: Pithayanukul
authors.forename: T
authors.initials: T
authors.lastname: Nagai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003564:Cytidine Deaminase / Q000378:metabolism*; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers; D005029:Ethylenediamines / Q000737:chemistry*; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008970:Molecular Weight; D012545:Schiff Bases / Q000138:chemical synthesis; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D004337:Drug Carriers; D005029:Ethylenediamines; D012545:Schiff Bases; D003561:Cytarabine; C068236:N(4)-(4-carboxybutyryl)-1-beta-arabinofuranosylcytosine; D003564:Cytidine Deaminase