Volume 8, Issue 5, October 2020, Page: 131-136
Investigation of Mechanism Activity of Antitumor and Radiosensitizing Activity of Preparations К-26 and K-26w
Adil Ahmedovich Ibragimov, Republican Specialized Scientific - Practical Medical Center of Oncology and Radiology, Laboratory of Synthesis of Antineoplastic Preparations, Tashkent, Uzbekistan
Zulfiya Mahmudovna Enikeeva, Republican Specialized Scientific - Practical Medical Center of Oncology and Radiology, Laboratory of Synthesis of Antineoplastic Preparations, Tashkent, Uzbekistan
Nigora Alimuhamedovna Agzamova, Republican Specialized Scientific - Practical Medical Center of Oncology and Radiology, Laboratory of Synthesis of Antineoplastic Preparations, Tashkent, Uzbekistan
Faizullo Saifyllaevich Salihov, The Bukhara Oncological Centre, Bukhara, Uzbekistan
Okiljon Abduhalilovich Rahimov, Republican Specialized Scientific - Practical Medical Center of Oncology and Radiology, Laboratory of Synthesis of Antineoplastic Preparations, Tashkent, Uzbekistan
Mavluda Turapovna Askarova, Department of Macroeconomic Analysis and Forecasting, Tashkent State Economic University, Tashkent, Uzbekistan
Received: Jul. 11, 2020;       Accepted: Jul. 28, 2020;       Published: Sep. 7, 2020
DOI: 10.11648/j.ajbls.20200805.12      View  23      Downloads  21
Abstract
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.
Keywords
К-26, K-26w, Sarcoma 180, Topoisomerase II, MDR2, p53, CFCs
To cite this article
Adil Ahmedovich Ibragimov, Zulfiya Mahmudovna Enikeeva, Nigora Alimuhamedovna Agzamova, Faizullo Saifyllaevich Salihov, Okiljon Abduhalilovich Rahimov, Mavluda Turapovna Askarova, Investigation of Mechanism Activity of Antitumor and Radiosensitizing Activity of Preparations К-26 and K-26w, American Journal of Biomedical and Life Sciences. Vol. 8, No. 5, 2020, pp. 131-136. doi: 10.11648/j.ajbls.20200805.12
Copyright
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Enikeeva Z. M., Kuznetsova N. N., Dimant I. N., Begisheva A. I, Sultanova D. Sh. 10-dezmetoksi-10 (N, N-bis (2-hydroxyethyl) amino)-7 (N- dezacetil) colchicine, possessing cytostatics action on cells of a cancer of a pancreas of the person and antimitotic effect in Russian. Patent UZ № 951C1 20000000, [UZC] 951, 2003.
[2]
Agzamova N. A., Enikeeva Z. M., Ibragimov A. A., Abdirova A. Ch, Tilljashajhov M. N. Studying of new derivatives colchicine К-26 and К-26-W on Ehrlich's Solid Tumor, the Sarcoma 180 and Walker carcinosarcoma in comparison with activity of some preparations in Russian. Eurasian Oncological Journal, Minsk, 2019, (7): 30-36.
[3]
Agzamova N. A., Enikeeva Z. M., Ibragimov A. A., Abdirova A. Ch, Tilljashajhov M. N. Comparison of activity of new derivatives colchicine К-26 and К-26w with activity taxol and etoposide, and also with preparations decovine and К-19 in Russian. Journal Medical Sciences, 2020, (1): 12-17.
[4]
Ibragimov A. A., Agzamova N. A., Karpysheva I. V., Ibragimov Sh. N., Enikeeva Z. M. Studying of activity of new antineoplastic preparation К-26w at different modes of introduction on strains sarcoma 180 and Walker carcinosarcoma in Russian. Journal Clinical and experimental oncology. Materials ХVI of scientifically practical conference. Multimodal therapy of malignant tumors, Tashkent, 2019, p. 227.
[5]
Enikeeva Z. M., Ibragimov A. A. New class cytostatics with stimulation colony-forming units on a spleen (CFCs) in Russian. Tashkent, Journal Fan va texnologiya, 2016, p. 173.
[6]
Enikeeva Z. M., Goloschapova J. A., Agzamova N. A., The radiosensibilizing activity of colchicine derivatives in Russian. Abstracts V the international Symposium on the Chemistry of natural compounds. 20-23 May 2003, Tashkent, Uzbekistan, p. 299.
[7]
Enikeeva Z. M., Golochapova J. A. Toxic and Antimitotic Property of a Series Colchicine Derivatives. Journal Chemistry of Natural Compounds, 1998, 32 (3): 343-344.
[8]
Maniatis T., Fritsch E. E., Sambrook J. In the Book: Molecular Cloning. A Laboratory Manual. Cold Spring Harbor Laboratory, 192, 480 P.
[9]
Campbell L., Abulrob A, Kandalaft K., Plummer S., Hollins A, Gibbs A, and Gumbleton M. Constitutive Expression of P-Glycoprotein in Normal Lung Alveolar Epithelium and Functionality in Primary Alveolar Epithelial Cultures. The Journal of Pharmacology and Experimental Therapeutics. 2003, 304 (1): 441–452.
[10]
Voronina E. I. Molecular-cellular and pathomorphology features in malignant lymphoma at display of a tumoral progression in the conditions of polychemotherapy in Russian. PhD dissertation thesis, Novosibirsk, 2014, 128 p.
[11]
Till J. E., Mc Culloch E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. J. Radiat. Res. 1961, 14 (1): 213-222.
[12]
Tevyashova A. N. Creation of prodrugs on a basis anthracycline antibiotics. Bulletin MITHT. Journal Chemistry and technology of drags preparations and biologically active connections in Russian. 2014, 9 (6): 11-25.
[13]
Gewirtz D. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin, J. Biochem. Pharmac. 1999, 57: 727–741.
[14]
Silverman R. Organic chemistry of drug design and drug action. San Diego: Elsevier Academic Press, 2004, 617 р.
[15]
Denny W. Emerging DNA topoisomerase inhibitors as anticancer drugs. J. Expert Opinion Emerg. Drugs, 2004, 9: 105–133.
[16]
Dezhenkova L. G., Cvetkov V. B, Shtil A. A. Ingibitory's topoisomerases I and II: chemical structure, mechanisms of action and a role in chemotherapy of tumors in Russian. Journal Advancement of chemistry, 2014, (83): 82-94.
[17]
Enikeeva Z. M., Nurullaeva D. Sh., Kuznecov N. N., Hashimova Z. S. Effect of Desacetilation on Statmokinetic Activity of Colchicine Derivatives. Journal Chemistry of Natural Compounds, 2002, 38 (6): 474-475.
[18]
Holin V. V. In the Book: Radio biological bases of radiation therapy of malignant tumours in Russian. Leningrad: Medicine, 1979, 387 P.
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