Осуществлен синтез лупановых С-28-имидазолидов, содержащих 3-оксо-, 3-гидроксиимино- и 2-циано-2,3-секо-4(23)-ен фрагменты в цикле А. При испытаниях in vitro наибольшую противоопухолевую активность показал 3-оксимино-луп-20(29)-ен-28-ил-1Н-имидазол-1-карбоксилат, значительно ингибируя рост или индуцируя гибель клеток рака легкого, толстой кишки, молочной железы, центральной нервной системы, яичника, простаты, почки, лейкозов и меланомы. В исследованиях на мышах наблюдали его умеренное противоопухолевое действие на перевиваемые аденокарциному молочной железы Ca755 и аденокарциному толстого кишечника AКАТОЛ.

In the Institute of experimental diagnostics and chemotherapy of FSBI «N.N. Blokhin CRC» RAMS a novel somatostatin analogue cifetrelin was synthesized. Cifetrelin has demonstrated antitumor activity on different experimental tumor models in vivo, including when orally administered. Taking this into account it seems to be worthwhile to investigate the possibility of development of cifetrelin drug formulation for oral delivery. We have offered a composition for cifetrelin drug formulation, that allows to obtain tablets that meet all State Pharmacopoeia XI requirements. It was determined that antitumor activity of cifetrelin in tablets is comparable with antitumor activity of cifetrelin substance when orally administered. It may be concluded that offered for cifetrelin oral drug formulation excipients do not reduce the cifetrelin release and antitumor activity.

In this study we have examined the activity of various drug formulations of mitoxantrone in vitro and in vivo. Our in vitro data indicated that the liposomal mitoxantrone was not as effective as free form of drug. However, in vivo animal models Ca-755 and P-388 the effect of liposomal form of mitoxantrone was much more promising in compare with free form of drug. The mitoxantrone formulations were injected into mice at a therapeutic dose regimen with a 96 h interval. The overall results of this study suggest that liposomal mitoxantrone increases the bioavailability of a preparation and reduces the dose for about 6-fold.

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.

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.