SYNTHESIS AND INVESTIGATION OF THE PHYSICOCHEMICAL PROPERTIES OF THE MECHANOCOMPOSITES OF ARABINOGALACTAN WITH CYCLOPHOSPHAMIDE

  • Надежда (Nadezhda) Анатольевна (Anatol'evna) Неверова (Neverova) Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033 Email: nadya_neverova@irioch.irk.ru
  • Елена (Elena) Николаевна (Nikolaevna) Медведева (Medvedeva) Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033 Email: woodemed@irioch.irk.ru
  • Василий (Vasilii) Анатольевич (Anatol'evich) Бабкин (Babkin) Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033 Email: babkin@irioch.irk.ru
  • Людмила (Liudmila) Ивановна (Ivanovna) Ларина (Larina) Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033 Email: larina@irioch.irk.ru
  • Анатолий (Anatolii) Николаевич (Nikolaevich) Сапожников (Sapozhnikov) Institute of Geochemistry. A.P. Vinogradov, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1а, Irkutsk, 664033 Email: sapozh@igc.irk.ru
  • Алексей (Aleksei) Александрович (Aleksandrovich) Левчук (Levchuk) Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033 Email: levchuk@irioch.irk.ru
  • Сергей (Sergei) Георгиевич (Georgievich) Кузьмин (Kuz'min) State Scientific Center "NIOPIK", ul. B. Sadovaya, 1, building 4, Moscow, 123001 Email: skuzmin@niopik.ru
Keywords: cyclophosphamide, larch arabinogalactan, mechanochemical treatment, mechanical composites, multi-nuclear NMR spectroscopy, X-ray diffraction analysis

Abstract

Methods of the creating systems for directional transport in the organism with the help of various carriers have recently been developed to improve the effectiveness and selectivity of the action of known drug substances (DS). Especially, the relevant problem is the toxicity reducing and selectivity increasing of antitumor DS. In recent years, studies are conducted on the creation of DS conjugates with natural polymers, in particular, with non-starch polysaccharides, many of which exhibit antitumor and immunomodulatory properties. Due to the unique combination of physico-chemical and biological properties, larch arabinogalactan (AG) is one of the most promising for the development of complex drugs with increased bioavailability and reduced toxicity.

The aim of this work is to obtain mechanocomposites of cyclophosphamide (CPA) with the initial (molecular weight 16645 Da) and fragmented (molecular weight 8380 Da) arabinogalactan and to study their physico-chemical properties.

According to IR and NMR 13C, 15N and 31P spectroscopy data, the long-term mechanochemical treatment does not lead to the change of the chemical composition of CPA molecules, only the formation of hydrogen bonds NH•••OH is observed. According to the data of X-ray diffraction analysis, IR and multi-nuclear NMR spectroscopy, the disordering of the crystal CPA structure and its molecular dispersion in the polysaccharide matrix without chemical interaction of the components are occurred during the mechanochemical treatment of CPA-AG mixtures at mass ratios of 1 : 5 and 1 : 10 for 4–12 hours.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Author Biographies

Надежда (Nadezhda) Анатольевна (Anatol'evna) Неверова (Neverova), Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033
Candidate of Sciences (Chemistry), Researcher
Елена (Elena) Николаевна (Nikolaevna) Медведева (Medvedeva), Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033
Candidate of Chemical Sciences, Senior Researcher
Василий (Vasilii) Анатольевич (Anatol'evich) Бабкин (Babkin), Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033
Doctor of Chemical Sciences, Head of the Laboratory of Wood Chemistry, Professor
Людмила (Liudmila) Ивановна (Ivanovna) Ларина (Larina), Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033
Doctor of Chemical Sciences, Leading Researcher
Анатолий (Anatolii) Николаевич (Nikolaevich) Сапожников (Sapozhnikov), Institute of Geochemistry. A.P. Vinogradov, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1а, Irkutsk, 664033
Candidate of Physical and Mathematical Sciences, Senior Researcher
Алексей (Aleksei) Александрович (Aleksandrovich) Левчук (Levchuk), Irkutsk Institute of Chemistry. A.E. Favorsky, Siberian Branch of the Russian Academy of Sciences, ul. Favorskogo, 1, Irkutsk, 664033
Candidate of Technical Sciences, Researcher
Сергей (Sergei) Георгиевич (Georgievich) Кузьмин (Kuz'min), State Scientific Center "NIOPIK", ul. B. Sadovaya, 1, building 4, Moscow, 123001
Head of Scientific Section

References

Duncan R. Nature Reviews Cancer, 2006, vol. 6, pp. 688–701.

Ivonin A.G., Pimenov E.V., Oborin V.A. i dr. Izvestiia Komi nauchnogo tsentra UrO RAN, 2012, no. 1(9), pp. 46–55. (in Russ.).

Gaikwad D., Dhawale Sh., Khandare J., Patil M., Khade T., Gavitre B., Bobe K., Kulkarni V., Gaikwad U. Research Journal of Pharmaceutical, Biological and Chemical Sciences, 2011, vol. 2, no. 2, pp. 200–208.

Elvira C., Gallardo A., San Roman J., Cifuentes A. Molecules, 2005, vol. 10, pp. 114–125.

Patent 2007/034495 (WO). 2007.

Il'ina A.V., Zubareva A.A., Kurek D.V. Rossiiskie nanotekhnologii, 2012, vol. 7, no. 1-2, pp. 84–89. (in Russ.).

Protsenko L.D., Bulkina Z.P. Khimiia i farmakologiia sinteticheskikh protivoopukholevykh preparatov: spravochnik. [Chemistry and Pharmacology of Synthetic Antitumor Preparations: A Handbook]. Kiev, 1985, 269 p. (in Russ.).

Perini P, Calabrese M, Rinaldi L, Gallo P. Expert Opinion on Drug Safety, 2007, vol. 6, pp. 183–190.

Dzhumabaeva B.T., Biriukova L.S. Gematologiia i transfuziologiia, 2015, vol. 60, no. 4, pp. 30–35. (in Russ.).

Morandi P., Ruffini P.A., Benvenuto G.M., Raimondi, Fosser V. Bone Marrow Transplant, 2005, vol. 35, pp. 323–334.

Xu X., Zhang X. Microbiological Research, 2015, vol. 171, pp. 97–106.

Kelly G.S. Alternative Medicine Review, 1999, vol. 4, no. 2, pp. 96–103.

Khotimchenko Iu.S. Biologiia moria, 2010, vol. 36, no. 5, pp. 319–328. (in Russ.).

Khotimchenko Iu.S. Biologiia moria, 2010, vol. 36, no. 6, pp. 399–409. (in Russ.).

Khotimchenko M.Iu. Efferentnaia terapiia, 2001, vol. 7, no. 4, pp. 22–36. (in Russ.).

Makker N.P., Hogan V., Honjo Y. et al. Journal of the National Cancer Institute, 2002, vol. 94, pp. 1854–1862.

Khotimchenko R.Iu. Razrabotka farmakologicheskikh sredstv na osnove nizkomolekuliarnykh pektinov i al'ginatov dlia antitoksicheskoi terapii: dis. … kand. biol. nauk. [Development of pharmacological agents based on low molecular weight pectins and alginates for antitoxic therapy: dis. ... cand. Biol. Sciences.]. Vladivostok, 2015, 145 p. (in Russ.).

Rybalkina O.Iu., Razina T.G., Lopatina K.A. i dr. Biulleten' eksperimental'noi biologii i meditsiny, 2012, vol. 154, no. 10, pp. 488–493. (in Russ.).

Rybalkina O.Iu., Ermakova N.N., Razina T.G. i dr. Biologiia moria, 2015, no. 5, pp. 366–373. (in Russ.).

Medvedeva E.N., Babkin V.A., Ostroukhova L.A. Khimiia rastitel'nogo syr'ia, 2003, no. 1, pp. 27–37. (in Russ.).

Patent 5544386 (US). 1996.

Kim L.S., Waters R.F., Burkholder P.M. Alternative Medicine Review, 2002, vol. 7, no. 2, pp. 138–149.

Medvedeva E.N., Babkin V.A., Makarenko O.A., Nikolaev S.M., Khobrakova V.B., Shulunova A.M., Fedorova T.E., Es'kova L.A. Khimiia rastitel'nogo syr'ia, 2004, no. 4, pp. 17–23. (in Russ.).

Patent 6011008 (US). 2000.

Dushkin A.V. Meteleva E.S., Tolstikova T.G., Tolstikov G.A., Poliakov N.E. Neverova N.A., Medvedeva E.N., Babkin V.A. Izvestiia RAN. Ser. Khim., 2008, no. 6, pp. 1274–1282. (in Russ.).

Babkin V.A., Medvedeva E.N., Neverova N.A., Levchuk A.A., Sapozhnikov A.N. Chemistry of Natural Compounds, 2014, vol. 50, no. 2, pp. 225–229.

Babkin V.A., Medvedeva E.N., Neverova N.A., Chipanina N.N., Aksamentova T.N., Meteleva E.S., Dushkin A.V. Materialy IV Vserossiiskoi nauchnoi konferentsii «Novye dostizheniia v khimii i khimicheskoi tekhnologii rastitel'nogo syr'ia». [Materials of the IV All-Russian Scientific Conference "New achievements in chemistry and chemical technology of plant raw materials"]. Barnaul, 2009, vol. 1, pp. 176–178. (in Russ.).

Tolstikova T.G., Khvostov M.V., Bryzgalov A.O., Dushkin A.V., Tolstikov G.A. Doklady akademii nauk, 2010, vol. 433, no. 5, pp. 713–714. (in Russ.).

Dushkin A.V., Tolstikova T.G., Khvostov M.V., Tolstikov G.A. The Complex World of Polysacchraids, ed. D.N. Karunaratn. Publisher: InTech, 2012, pp. 573–602.

Medvedeva E.N., Neverova N.A., Fedorova T.E., Babkin V.A., Meteleva E.S., Dushkin A.V., Tolstikova T.G., Khvostov M.V., Dolgikh M.P. Khimiia rastitel'nogo syr'ia, 2009, no. 3, pp. 49–56. (in Russ.).

Prescott J., Enriquez P.M., Chu Jung, Menz E.T., Groman E.V. Carbohydrate Research, 1995, vol. 278, pp. 113–128.

Ponder G.R., Richards G.N. Journal of Carbohydrate Chemistry, 1997, vol. 16, no. 2, pp. 195–211.

Ponder G.R., Richards G.N. Carbohydrate Polymers, 1997, vol. 34, no. 4, pp. 251–261.

Dushkin A.V., Meteleva E.S., Tolstikova T.G., Pavlova A.V., Khvostov M.V. Khimiko-farmatsevticheskii zhurnal, 2012, no. 7, pp. 70–73. (in Russ.).

Medvedeva E.N., Fedorova T.E., Vanina A.S., Rokhin A.V., Es'kova L.A., Babkin V.A. Khimiia rastitel'nogo syr'ia, 2006, no. 1, pp. 25–32. (in Russ.).

Published
2017-10-12
How to Cite
1. Неверова (Neverova)Н. (Nadezhda) А. (Anatol’evna), Медведева (Medvedeva)Е. (Elena) Н. (Nikolaevna), Бабкин (Babkin)В. (Vasilii) А. (Anatol’evich), Ларина (Larina)Л. (Liudmila) И. (Ivanovna), Сапожников (Sapozhnikov)А. (Anatolii) Н. (Nikolaevich), Левчук (Levchuk)А. (Aleksei) А. (Aleksandrovich), Кузьмин (Kuz’min)С. (Sergei) Г. (Georgievich) SYNTHESIS AND INVESTIGATION OF THE PHYSICOCHEMICAL PROPERTIES OF THE MECHANOCOMPOSITES OF ARABINOGALACTAN WITH CYCLOPHOSPHAMIDE // Chemistry of plant raw material, 2017. № 1. P. 37-44. URL: https://journal.asu.ru/cw/article/view/2986.
Section
Biopolymers of plants