title: [Biotransformation of 1-beta-D-ribofuranosyl-4-methylthiopyrazolo(3,4-d)pyrimidine and its 5'-monophosphate].
abstract: 1-beta-D-Ribofuranosyl-4-methylthiopyrazolo(3,4-d)pyrimidine (I) has been converted into its 5'-monophosphate (III) by reacting with POCl3 in trialkyl phosphates or by phosphorylating 2',3'-O-ethoxymethylidene derivative of riboside (I) using 2-cyanoethyl phosphate in the presence of DCC and subsequent removal of blocking groups. Condensation of nucleotide (III) imidazolide with pyrophosphoric acid afforded corresponding 5'-triphosphate. Pools of natural NTPs and riboside (I) phosphates were monitored by HPLC after administering riboside (I), phosphate (III), or 4-methylthiopyrazolo(3,4-d)pyrimidine (II) into mice with leukemia L1210 or after incubating CaOv culture cells with these compounds. Treatment with riboside (I) or nucleotide (III) possessing antileukemic and cytotoxic activites led to much higher level of monophosphate (III), than treatment with biologically inactive base (II). ATP and GTP levels in CaOv cells incubated with (I) or (III) decreased by 60-70%, whereas (II) did not affect NTP pool. Bioactivation of nucleoside (I) into monophosphate (III) proceeds via direct phosphorylation by adenosine kinase. No tranformation of (II) into (I) or (III) occurs under these conditions.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000378:metabolism*; D001711:Biotransformation; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D006801:Humans; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D010051:Ovarian Neoplasms / Q000378:metabolism; D013872:Thionucleosides / Q000138:chemical synthesis / Q000378:metabolism*; D013873:Thionucleotides / Q000138:chemical synthesis / Q000378:metabolism*
chemical_list: C043404:1(beta)-ribofuranosyl-4-(methylmercapto)pyrazolo(3,4-d)pyrimidine 5'-monophosphate; D000970:Antineoplastic Agents; D013872:Thionucleosides; D013873:Thionucleotides; C043416:1 beta-ribofuranosyl-4-(methylmercapto)pyrazolo(3,4-d)pyrimidine
vernacular_title: Biotransformatsiia 1-beta-D-ribofuranozil-4-metilmerkaptopirazolo (3,4-d)pirimidina i ego 5'-monofosfata.