STUDYING THE ACUTE TOXICITY AND ANTI-TUMOR ACTIVITY OF THE NEW DRUG COLHAMETIN
Yuldashev Javlonabduraimovich , Samarkand State Medical University, Uzbekistan Ibragimov Shavkat Narzikulovich , Republican Specialized Scientific And Practical Medical Center Of Oncology And Radiology Of The Ministry Of Health Of The Republic Of Uzbekistan Shakhanova Shakhnoza Shavkatovna , Samarkand State Medical University, Uzbekistan Esankulova Bustonoy Sobirovna , Samarkand State Medical University, UzbekistanAbstract
The aim of the study was to study acute toxicity during intraperitoneal administration of a new antitumor drug "colhametin" (K-2) in mice and rats and its antitumor activity on 2 strains of tumors, including with a smaller number of injections.
Material and research methods. Acute toxicity of the K-2 preparation after a single intraperitoneal injection was carried out according to the Litchfield and Wilcoxon method on 30 white outbred mice weighing 20±2g of both sexes and 30 male and female rats weighing 140±10g, 5 animals in each group. The study of antitumor activity was performed on 12 outbred mice and 16 outbred rats with transplanted tumors S-180 (Sarcoma-180) and WC (Walker's sarcoma) which were administered drugs on the 4th day after tumor inoculation 10- and 5-fold. The results were evaluated according to standard criteria: tumor growth inhibition (TGI), body weight and spleen of animals Differences were considered significant at p<0.05.
Results. The following data were obtained with a single intraperitoneal injection to mice: the average lethal dose of LD50 is 890 (-150 + 172) mg/kg, LD50 with a single intraperitoneal dose of K-2 preparation in rats, LD50 is 410 (-56 + 61) mg/kg, the values are also determined LD10, LD16 and LD84.
The antitumor activity of the drug K-2 on the tumor strain Sarcoma - 180 was high, 99/90%. On WC tumors the effect of K-2 reached 90/91% with 10-fold administration, and 89/89% with 5-fold administration, however, its effect was accompanied by a decrease in hematopoietic parameters.
Conclusions. The study of the acute toxicity of the substance of the preparation K-2 showed that this preparation belongs to the IV class of low-toxic compounds. On 2 tumors, the effect of the new drug was high, which did not decrease with a decrease in the number of injections.
Keywords
New anticancer drug colhametin, acute toxicity, mice
References
Guidelines for the chemotherapy of neoplastic diseases. Ed. N.I. Perevodchikov. "Practical Medicine". Moscow 2013.
Igarashi K., Kawaguchi K., Li S., Qinghong Han Q., Tan Y., et al. Recombinant methioninase combined with doxorubicin (DOX) regresses a DOX-resistant synovial sarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model // Oncotarget. – 2018. – Vol.9. – N 27. – P. 19263-19272.
Hirai F., Yamanaka T., Taguchi K., Daga H., Ono A., Tanaka K., Kogure Y., Shimizu J., Kimura T., Fukuoka J., Iwamoto Y., Sasaki H., Takeda K., Seto T., Ichinose Y., Nakagawa K., Nakanishi Y. A multicenter phase II study of carboplatin and paclitaxel for advanced thymic carcinoma: WJOG4207L //Annals of Oncology. –2015. –N26. –P. 363–368.
Dapeng Y., Shuisheng Z., Alei F., Deguo X., et al. Methotrexate, doxorubicin, and cisplatinum regimen is still the preferred option for osteosarcoma chemotherapy. Medicine 98 (19): p e15582, May 2019.
Sasada S., Kodaira M., Shimoi T., Shimomura A., Yunokawa M., et al. Ifosfamide and Etoposide Chemotherapy in the Treatment of Recurrent/Refractory Rhabdomyosarcoma in Adults. (2016) Anticancer Research 36: 2429-2432.
Shavkatovna, S. S., Maxammatkulovich, R. N., & qizi, S. N. A. (2022). Breast Pathology in Adolescent Girls. Central Asian Journal of Medical and Natural Science, 3(3), 66-71. https://doi.org/10.17605/OSF.IO/MVD63
Enikeeva Z.M., Ibragimov A.A. A new class of cytostatics with stimulation of colony-forming units on the spleen (CFUs). In book: Monograph. Tashkent - 2016, from "Fan va texnologiya", 173p.
Ibragimov A.A., Enikeeva Z.M., Agzamova N.A., Salihov F. S., Rahimov O.A., Askarova M.T. Investigation of Mechanism Activity of Antitumor and Radiosensitizing Activity of Preparations К-26 and K-26w // American Journal of Biomedical and Life Sciences. – 2020. – Vol.8. – N 5. – P. 131-136.
Enikeeva Z.M., Ibragimov A.A., Agzamova N.A., Vypova N.L., Saidhodjaeva S.S., Kholturaeva N.R., Abdirova A.Ch., Tuychiev O.D., Polatova J.Sh., Kadirova D.A., Salihov F.S. Study of the Antitumor Activity of the Drug Dekoglitz on Two Tumors and Some Aspects of Its Mechanism of Action // Journal of Oncology Research. – 2021. –Vol.3. –N 1. – P. 11-16.
Ibragimov Sh.N., Enikeeva Z.M., Abdukhalilov M.M., Saidkulov B.S., Narzikulova K.Sh. The study of mitotic activity, alkulating action end effect on topoisomerase preparations K-19, decovin and K-20, obtained on the basis of colchicine and colchamine // European Science Review. 2018. – N7-8. –P.103-106.
Enikeeva Z.M. Sulfur-containing Aminoacid Derivatives of Colchicine and Colchamine and Derivatives of Izothiouronium and Mercaptoethilamine. Chemistry of Natural Compounds, 1998, V.35, No. 5, p. 556-563.
Enikeeva Z.M., Fuzailova T.M., Ibragimov Sh.N., Umarov M., Kholturaeva N.R., Karpysheva I.V. Study of the antitumor activity of the drug K-2 in the early periods after inoculation of tumors in mice (communication 1). Pharmaceutical journal. Tashkent-2017, No. 3. pp.103-107.
Guidelines for preclinical study of the general toxic effect of drugs. In book: Guidelines for conducting preclinical studies of drugs. Part one. pp.13-23. Edited by A.N. Mironov, Moscow-2012, p.944.
Cidorov K.K. Toxicology of new industrial chemicals. Moscow.: Medicine, 1973, Issue 3. 47p.