New preparation’s obtaining on the base of the chemical-biological adduct of bis-[5-bromopyrimidine-2',4'-diono-1'-il]-2-bromo-2'-chloroethylene and bacterial lectin, investigation of its activity on sarcoma 45
With a purpose of new potential antitumour preparation’s obtaining method of synthesis of new bis-derivative of 5-bromouracile was developed, the chemical-biological adduct on the base of 1,1-bis-[5-bromopyrimidine-2',4'-diono-1'-il]-2-bromo-2'-chloroethylene and antitumour bacterial lectin Bacillus polymyxa was produced.
Object of investigation is a new bis-derivative of 5-bromouracile which synthesised on the base of substituted pyrimidine and halothane. Investigation of critical toxicity of new compound was carried out at SO «Institute of Pharmacology and Toxicology of NAMS of Ukraine». The lectin’s preparations were obtained by treatment of culture Liquid of saprophytic strain Bacillus from Ukrainian Collection of Microorganisms of Zabolotnyi Institute of Microbiology and Virology of NAS of Ukraine. The white imbredical mice and experimental model of tumor growth – cancer Sarcoma 45, were used following published procedures in Prozorovskiy. The experimental tumor used for our investigation were obtained from Strain Bank of Oncological Centre of Russian Academy of Medical Sciences. Molecular complex of bis-adduct and bacterial lectin was obtained by mixing two components at physiological solution, 1:1.
It was discovered that chemical-biological adduct of bis-derivative of 5-bromouracile and bacterial lectin applies to a little toxic preparation (LD50 = 635 mg/kg) and demonstrates considerable antitumour effect upon to 82,0% on Sarcoma 45 tumour. It confirms that new chemical-biological adduct is perspective for the future investigation as substance with a little toxicity and high antitumour activity on the Sarcoma 45.
Anti-tumor activity of molecular complexe of bis-derivative of 5-bromouracile and Bacillus polymyxa 102 KGU permits us to consider it as physiological active with a perspective investigation as a potential antitumor drug for future treatment in people. The construction of the principle of new medical preparations on the basis of the saprophytic strains bacterial lectins and heterocyclic bis-adducts is very possible.
2. Karacuba T. A., Sharikina N. I., Sheglov V. I. ta in. Suchasni mozhlivosti vplivu farmakoterapiyi na rist ta procesi metastazuvannya zloyakisnih puhlin // Tam samo. – 2002. – T. 1, № 3–4. – S. 3–6.
3. Kudryavceva I. G., Sharikina N. I. Suchasnij stan poshuku i vivchennya FAR z protipuhlinnoyu diyeyu sered pohidnih kisloti fosforu // Tam samo. – 2004. – № 1–2. – S. 31–40.
4. Aschele C., Debermardis D. et al. Thymidilate synthase protein expression in colorectal cancer metastases predicts for clinical outcome to leucovorinmodulated lobus or infusional 5-fluorouracil but not methotrexate – modulates lobus 5-fluorouracil // Ann. Oncol. – 2002. – V. 13. – P. 1882–1892.
5. Twelves C., Boyer M., Findlay M. et al. Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma // Eur. J. Cancer. – 2001. – V. 37. – P. 597–604.
6. Baba H., Kohnoe S., Endo K. (Eds.) State of the treatment for gastrointestinal cancer // Gan To Kagaku Ryoho. – 2000. – V. 27. – P. 1233–1246.
7. Kleckij M. E., Cupak E. B., Nazarov D. A. Struktura i reakcionnaya sposobnost proizvodnyh uracila // HGS. – 2002. – № 8. – S. 1106–1108.
8. Noordhuis P., Holwerda U. 5-fluorouracil incorporation info RNA and DNA in relation to thymidilate synthetase inhibition human colorectal cancer // Ann. Oncol. – 2004. – V. 15. – P. 1025–1032.
9. Longley D. B., Harkin D. P. Mechanisms of action of 5-fluorouracil // Nat. Rev. Cancer. – 2004.– V. 4. – P. 230–238.
10. Sofina Z. P., Syrkin A. B., Goldin A., Klyajn A. Eksperimentalnaya ocenka protivoopuholevyh preparatov v SSSR i SShA. – M.: Medicina, 1979. – 296 s.
11. Prozorovskij V. B., Prozorovskij V. P., Demchenko V. M. Ekspress metod opredeleniya srednej effektivnosti dozy i ee oshibki // Farmakol. toksikol. – 1978. – T. 41, № 4. – S. 407–509.
This work is licensed under a Creative Commons Attribution 4.0 International License.