Abstract
In this work, a water-soluble supramolecular complex was synthesized in an aqueous suspension of betulin diacetate (BDA) and arabinogalactan (AG) upon microwave heating. Microwave heating allows reducing the time required for the complex formation, compared with conventional heating in a water bath. The specific effect of microwave irradiation on the initial reagents and preparation of a supramolecular complex was studied. In contrast to conventional heating, under microwave heating AG macromolecules may break into roughly equal fragments when the temperature increases up to 100 °C. A change in the surface morphology of BDA crystals under microwave heating of the suspension suggests that microwave irradiation facilitates the dissolution of BDA in water. It has been shown that the use of dimethylsulfoxide as a reaction medium for microwave heating led to a decrease in BDA content in the product due to the inclusion of DMSO into AG macromolecules. The BDA–AG complex was isolated from the microwave-heated aqueous solution, after water evaporation, as a thin amorphous film, which exhibited antitumor activity against Ehrlich ascites carcinoma cells and can be a promising material for pharmacological applications.
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References
Alexandre F-R, Domon L, Frère S, Testard A, Thièry V, Besson T (2003) Microwaves in drug discovery and multi-step synthesis. Mol Divers 7:273–280. https://doi.org/10.1023/B:MODI.0000006860.56083.2b
Bandyopadhyay D, Banik BK (2015) Chapter 19—microwave-induced synthesis of heterocycles of medicinal interests. In: Brahmachari G (ed) Green synthetic approaches for biologically relevant heterocycles. Elsevier, Amsterdam, pp 517–557. https://doi.org/10.1016/B978-0-12-800070-0.00019-0
Butyagin P (2000) Mechanochemical synthesis: mechanical and chemical factors. J Mater Synth Process 8:205–211. https://doi.org/10.1023/A:1011316227193
Chakraborty B, Dutta D, Mukherjee S, Das S, Maiti NC, Das P, Chowdhury C (2015) Synthesis and biological evaluation of a novel betulinic acid derivative as an inducer of apoptosis in human colon carcinoma cells (HT-29). Eur J Med Chem 102:93–105. https://doi.org/10.1016/j.ejmech.2015.07.035
Doehler D, Peterlik H, Binder WH (2015) A dual crosslinked self-healing system: supramolecular and covalent network formation of four-arm star polymers. Polymer 69:264–273. https://doi.org/10.1016/j.polymer.2015.01.073
Dushkin AV, Tolstikova TG, Khvostov MV, Tolstikov GA (2012) Complexes of polysaccharides and glycyrrhizic acid with drug molecules—mechanochemical synthesis and pharmacological activity. In: Karunaratne DN (ed) The complex world of polysaccharides. InTech, Rijeka, pp 573–602. https://doi.org/10.5772/48182
Kappe CO (2004) Controlled microwave heating in modern organic synthesis. Angew Chem Int Ed 43:6250–6284. https://doi.org/10.1002/anie.200400655
Kuznetsova SA, Kuznetsov BN, Mikhailov AG, Skvortsova GP (2006) The method of obtaining arabinogalactan. RU Patent 2273646, Apr 10, 2006; Chem Abstr 2006:333535
Kuznetsova SA, Kuznetsov BN, Red’kina ES, Sokolenko VA, Skvortsova GP (2008) The method of obtaining betulin diacetate. RU Patent 2324700, May 20, 2008; Chem Abstr 2008:605472
Kuznetsova SA, Malyar YuN, Shakhtshneider TP, Mikhailenko MA, Drebushchak VA, Boldyrev VV (2013) Mechanochemical preparation of the composites of betulin esters with arabinogalactan and investigation of their physicochemical properties. Chem Sustain Dev 21:609–614
Li J, Nagamani C, Moore JS (2015) Polymer mechanochemistry: from destructive to productive. Acc Chem Res 48:2181–2190. https://doi.org/10.1021/acs.accounts.5b00184
Lu F (2013) Preparation of lupane triterpenoid derivatives and pharmaceutical use thereof. WO Patent 2013117137, Aug 15, 2013; Chem Abstr 2013:1266358
Mikhailenko MA, Shakhtshneider TP, Eltsov IV, Kozlov AS, Kuznetsova SA, Karacharov AA, Boldyrev VV (2016) Supramolecular architecture of betulin diacetate complexes with arabinogalactan from Larix sibirica. Carbohydr Polym 138:1–7. https://doi.org/10.1016/j.carbpol.2015.11.047
Olubambi PA, Potgieter JH, Hwang JY, Ndlovu S (2007) Influence of microwave heating on the processing and dissolution behaviour of low-grade complex sulphide ores. Hydrometallurgy 89:127–135. https://doi.org/10.1016/j.hydromet.2007.07.010
Pistarà V, Rescifina A, Chiacchio MA, Corsaro A (2014) Use of microwave heating in the synthesis of heterocycles from carbohydrates. Curr Org Chem 18:417–445. https://doi.org/10.2174/13852728113176660146
Prieto P, de la Hoz A, Díaz-Ortiz A, Rodríguez AM (2017) Understanding MAOS through computational chemistry. Chem Soc Rev 46:431–451. https://doi.org/10.1039/c6cs00393a
Shakhtshneider TP, Kuznetsova SA, Mikhailenko MA, Zamai AS, Malyar YuN, Zamai TN, Boldyrev VV (2013) Effect of mechanochemical treatment on physicochemical and antitumor properties of betulin diacetate mixtures with arabinogalactan. Chem Nat Compd 49:470–474. https://doi.org/10.1007/s10600-013-0641-x
Shakhtshneider TP, Kuznetsova SA, Zamay AS, Zamay TN, Spivak EA, Mikhailenko MA, Malyar YuN, Kuznetsov BN, Chesnokov NV, Boldyrev VV (2016) New composites of betulin esters with arabinogalactan as highly potent anti-cancer agents. Nat Prod Res 30:1382–1387. https://doi.org/10.1080/14786419.2015.1060591
Singh S, Gupta D, Jain V, Sharma AK (2015) Microwave processing and applications in manufacturing industries: a review. Mater Manuf Processes 30:1–29. https://doi.org/10.1080/10426914.2014.952028
Suman P, Patel A, Solano LN, Jampana G, Gardner Z, Holt CM, Jonnalagadda SC (2017) Synthesis and cytotoxicity of Baylis-Hillman template derived betulinic acid-triazole conjugates. Tetrahedron 73:4214–4226. https://doi.org/10.1016/j.tet.2016.11.056
Tsukahara Y, Higashi A, Yamauchi T, Nakamura T, Yasuda M, Baba A, Wada Y (2010) In situ observation of nonequilibrium local heating as an origin of special effect of microwave on chemistry. J Phys Chem C 114:8965–8970. https://doi.org/10.1021/jp100509h
Wang H, Maxim ML, Gurau G, Rogers RD (2013) Microwave-assisted dissolution and delignification of wood in 1-ethyl-3-methylimidazolium acetate. Bioresour Technol 136:739–742. https://doi.org/10.1016/j.biortech.2013.03.064
Acknowledgements
The reported study was funded by the Russian Foundation for Basic Research (Project no. 16-33-50137) and by RFBR and Government of the Krasnoyarsk Territory (Project no. 16-43-242083).
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Malyar, Y.N., Mikhailenko, M.A., Pankrushina, N.A. et al. Microwave-assisted synthesis and antitumor activity of the supramolecular complexes of betulin diacetate with arabinogalactan. Chem. Pap. 72, 1257–1263 (2018). https://doi.org/10.1007/s11696-017-0362-x
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DOI: https://doi.org/10.1007/s11696-017-0362-x