Aim: Evaluation of the antitumor activity of the new drug Dekoglitz in animals with tumor strains of Sarcoma 45 in comparison with the drug dekocin, from which it was obtained, as well as with 5-fluorouracil and etoposide, and on ovarian tumors (OT) in comparison with the drug dekocin and identification of the effect of Dekoglitz on NA synthesis and internucleosomal DNA degradation. Methods: The study of preparations was carried out on 68 outbred rats with transplanted C-45 and OT tumors. The alkylating effect of the drugs was studied on cells tumor of Sarcoma 180. Results: The antitumor activity of dekoglitz on Sarcoma 45 was high, about 98/96%, with a remission rate of 80%. Its effect was 28-24% higher than that of dekocin. On OT, the effect of decoglitz with intraperitoneal administration reached 89/76% with a remission rate of 40%, with oral administration 96/86% with a remission rate of 60%. Conclusion: The study of the new drug Dekoglitz on animals with a tumor of Sarcoma 45 revealed its higher activity (by 20-27%) in comparison with the original Dekocin, 5-fluorouracil and etoposide with a lower level of side effects. On OT, the effect of Dekoglitz was 35-40% higher, especially after oral administration. Apparently, the great ability to suppress the synthesis of NA and carry out internucleosomal degradation and fragmentation of tumor DNA by the new drugs dekoglitz explains its antitumor efficacy, which is greater than that of Dekocin (K-18) in experiments on tumors.

Introduction. Tropolone alkaloid -colchicine, there is very interesting object for synthesis of its derivatives, with such properties as, alkylation, a low toxicity, high antineoplastic activity and especially overcoming of multidrug resistance (MDR). We had been developed the antineoplastic preparation К-26 derivative of colchicine. К-26 has shown high cytotoxic activity on 60 lines of tumoral cells of the human in vitro, at National Institute of the Cancer of the USA (NCI). Further on the basis of К-26 its water-soluble form named term К-26w has been received. The work purpose. Studying of the mechanism of action of preparations К-26 and К-26w on: alkylating ability, mitotic activity, topoisomerase II, MDR2, р53 and colony-forming cells spleen (CFCs). Materials and methods. All researches have been carrying out by a standard technique. Studying mitotic activity of preparations was carrying out on duodenum and tumor СаРа after preparation influence. On models of a tumor of the Sarcoma 180 action of preparations has been investigated: the alkylating -on synthesis DNA/RNA, nucleosoma DNA degradation, activity topoisomerase II; on an expression MDR2 and р53 genes. Studying CFCs carry out by a standard technique on outbred mice. Results. К-26, К-26w and etoposide inhibited in cells of the Sarcoma 180: synthesis DNA/RNA on 84/65%, 95/85% and 55/35%, accordingly, in relation to the control; activity topoisomerase II on 80%, 90% and 60% accordingly. By method RT-PCR it is shown, К-26, К-26w and etoposide: inhibited an expression of MDR2 gene on 83%, 91% and 62%; increase expression р53 gene to 74%, 88% and 55%, accordingly, under the relation of the control of referential gene GARDH (100%). High ability К-26 and К-26w in an induction apoptosis tumoral cells and CFCs to 12 units is shown. Conclusion. Revealed ability К-26 and К-26w to suppress synthesis DNA/RNA activity topoisomerases, to stimulate р53, and also to suppress an expression of a multidrug resistance MDR2 gene, it explains their high antineoplastic activity which is connected with mitotic activity leading to cell fission synchronization, and radiosensitization activity. Special interest represents found at К-26w and К-26 suppression MDR2 as they are aimed for treatment of such resistant tumor as a kidney cancer. Stimulation CFCs which provides formation of haemopoetic and immune cells can protect an organism from their intensive cytotoxic action.

New antineoplastic preparations К-26 and К-26-w have been created on a basis of alkaloid colchicines, which were studied in animals with common tumors in comparison with commercial preparations taxol, vincristine and etoposide, and also with earlier developed derivatives colchicine and colchamine К-19 and decovine. The experiments were conducted on 60 outbred mice with Ehrlich’s solid tumor and the Sarcoma 180 and in 32 outbred rats with Carcinosarcoma Walker. All drugs are administered in therapeutic doses 8-fold mode on the 10th day and on the 3rd day after tumor subinoculation. Estimated results are obtained according to standard provisions. A study of preparations К-26 and К-26-w in animals with tumors has revealed their more expressed activity compared to taxol, vincristine, and etoposide; the activity of these preparations is 4-10% lower than the actions К-19 and dekovine, but causing a decrease in the number of leukocytes. The lower level of side effects is explained by the greater ability to induce К-26 compared to К-19 and dekovine.

The new colchicine derivative ‘K-26’ manifested both high cytotoxic activity in vitro at the National Cancer Institute of the USA (NCI) and high antitumor activity in a number of transplanted animal tumors. The high antitumor activity of the K-26, as well as its further study as a radiation sensitizer, suggests the study of the alkylating action (effect on DNA and RNA synthesis, on internucleosomal degradation and DNA fragmentation), impact on topoisomerase II activity and drug resistance as well as mitotic activity and induction of CFU. The study showed that K-26 inhibits DNA synthesis, the activity of topoisomerases and MDR2. It stimulates p53, which explains its high antitumor and mitotic effect, leading to the synchronization of cell division and radiation-sensitizing activity. Stimulation of CFEC, which ensures the formation of hematopoietic and immune cells, can protect the body from its intense cytotoxic effect.

Цель работы. Оценка противоопухолевой активности нового препарата колхицинола-2 (К-26-в) на животных с опухолевым штаммом солидная опухоль Эрлиха (СОЭ) в разные периоды после перевивки, а также при разных путях введения.Материалы и методы. Изучение выполнено на 86 беспородных мышах с перевиваемой опухолью СОЭ. К-26-в вводили мышам на 3, 5 и 10-й день после перевивки опухоли 10- и 8-кратно в/б в разных дозах, в сравнении с К-26, а также при разных путях 10-кратного введения через 6 дней после перевивки. Оценку результатов проводили по стандартным критериям: торможение роста опухоли (ТРО), масса тела и селезенки животных. Достоверными считали различия при р<0,05.Результаты. К-26-в в дозе 32 мг/кг на опухоли СОЭ проявил активность на 3-й и 5-й дни после перевивки в 93–98%, через 10 дней после перевивки был эффективен на 95%. При разных способах введения лечение К-26-в вызвало следующий результат: при подкожном введении эффект составлял 98/97%, внутримышечном – 93/93%, внутрибрюшинном – 88/87% и внутривенном – 82/83% (по объему и массе опухоли). Во всех опытных группах не было гибели животных, депрессии массы тела и селезенки.Заключение. К-26-в оказался высокоактивным в отношении опухоли СОЭ, уровень ТРО=93– 98% как в раннем периоде, так и в отсроченном при влиянии на развившиеся опухоли (с эффектом в 95%). При изучении лучшего пути введения нового препарата показано, что наиболее предпочтительный способ введения – внутримышечное или подкожное введение с эффектом в 93–98%, которое рекомендовано для проведения клинических испытаний. Purpose. Evaluation of the antitumor activity of the new preparation colchicinol-2 (K-26-w) in animals with the tumor strain Ehrlich's solid tumor (EST) in different periods after inoculation, as well as in different routes of administration.Materials and Methods. The study was carried out on outbred mice with the transplanted EST tumor. K-26-w was injected into mice on the 3rd, 5th, and 10th days after tumor inoculation, 10 and 8 times intraperitoneally at different doses, in comparison with K-26, as well as in different routes of 10-time administration in 6 days after inoculation. The results were assessed according to the standard criteria: tumor growth inhibition (TGI), weight of the body and spleen of animals. The differences were considered significant in p<0.05.Results. K-26-w in the dose of 32 mg/kg showed the activity on the 3rd day after inoculation (the activity was 93–98%); in 10 days after inoculation, it was 95% effective. In different methods of administration, the treatment with K-26-w caused the following result: in subcutaneous administration, the effect was 98/97%, intramuscular administration – 93/93%, intraperitoneal – 88/87%, and intravenous – 82/83% (by volume and weight of tumor). In all experimental groups, there was no death of animals, depression of body weight and spleen.Conclusion. K-26-w proved to be highly active in EST tumors; TGI level=93–98% both in the early period and in the delayed period, with the effect on the developed tumors (with the effect of 95%). When studying the best route of administration of a new drug, it was showed that the best routes of administration are intramuscular or subcutaneous ones with the effect of 93–98%, which is recommended for clinical trials.