[Synthesis and biological properties of pyrimidine 2'-deoxynucleosides modified by a residue of quinaldic acid]. / Sintez i biologicheskie svoistva pirimidinovykh 2'-dezoksinukleozidov, modifitsirovannykh ostatkom khinal'dinovoi kisloty.

O-Quinaldoyl derivatives of thymidine, 2'-deoxyuridine, and 5-trimethylsilyl-2'-deoxyuridine were synthesized. 5'-Deoxy-5'-(quinoline-2-carbonylamino)- and 5'-deoxy-5'-[(quinoline-2-carbonylamino)butyroylamino]thymidine were obtained by the reaction of 5'-amino-5'-deoxythymidine with pentafluorophenyl ester of quinaldic acid, or with 4-(quinoline-2-carbonylamino)butyric acid. Antiproliferative properties in respect to CaOv cells in vitro were found in most of the synthesized quinaldoyl derivatives of nucleosides (CE50 approximately 10(-5) M). 3'-O-Quinaldoylthymidine exhibited an antitumor activity in vivo. The interaction of 3'- and 5'-O-quinaldoyl- as well as 3',5'-di-O-quinaldoylthymidine with DNA was investigated by the method of fluorescent probes.

[Synthesis, conversion and biological activity of 5-substituted 2'-deoxyuridines modified by carbohydrates]. / Sintez, prevrashcheniia i biologicheskaia aktivnost' modifitsirovannykh po uglevodu 5-zameshchennykh 2'-dezoksiuridinov.

5-Benzyloxymethyl(Bom)-2'-deoxyuridine and its alpha-anomer were used as the key compounds for syntheses of thymidine analogues or 3'-derivatives. Anomeric 5-Bom-2'-deoxyuridines were synthesized from 5-Bom-uracil and 2-deoxy-3,5-di-O-p-toluyl-alpha-D-ribo-furanosyl chloride by means of the silyl method. 5-Bom-2'-deoxyuridine was transformed successively to 3',5'-di-O-mesyl derivative, 2,3'-anhydro-1-(2-deoxy-5-O-p-toluyl-beta-D-xylofuranosyl)-5-Bom-uracil and 3'-azido-2',3'-dideoxy-5-Bom-uridine. Treatment of the last with SnCl4 in methylene dichloride--methanol led to 3'-azido-2',3'-dideoxy-5-methoxymethyluridine. Under the same conditions the 5-methoxymethyl derivative was obtained from 3',5'-di-O-p-toluyl-5-Bom-2'-deoxyuridine. Interaction of 1-(2-deoxy-alpha-D-ribofuranosyl)-4-Bom-uracil with SnCl4 in methylene dichloride as well as the hydrogen transfer hydrogenolysis in the presence of cyclohexene and Pd(OH)2/C in ethanol led to 1-(2-deoxy-alpha-D-ribofuranosyl)-5-hydroxymethyluracil. Only 3'-azido-2',3'-dideoxy-5-Bom-uridine showed a cytotoxic activity against CaOv cells in vitro: in 10(-5)-10(-4) M concentrations it inhibits the thymidine incorporation into DNA by 78.8-95.1%. Elucidation of antitumor activity in vivo showed that this nucleoside inhibits growth of solid tumours, Ca755 and LLC, by 79 and 79-83%, respectively, but has no therapeutic effect against lympholeukemia P388.

[Antineoplastic activity of combinations of cytostatics and dextran-ferrite administered to mice with leukemia P-388]. / Protivoopukholevaia aktivnost' kompozitsii tsitostatikov s dekstran-ferritom pri vvedenii mysham s leikozom P-388.

Water solutions of adriblastin, dactinomycin, rosevin, methotrexate, cisplatin, sarcolysine, rubomycin, cyclophosphamide, 5-fluorouracil or ftorafur were combined with dextran ferrite. The obtained compositions were injected i.p. to BDF1 mice 24 hours after they were inoculated with one million of murine P388 leukemic cells. Antitumor activity was fully retained for each of these agents in combination with dextran ferrite.