MASS SPECTROMETRY OF SUPRAMOLECULAR COMPLEXES OF GLYCYRRHETINIC ACID WITH ANTIBIOT-ICS STREPTOTSID
Abstract
One of most effective ways to increase the bioavailability of drug substances is their structural modification by formation of supramolecular structures with plant glycosides. Application of noncovalent complexes of drugs with plant glycosides, e.g., glycyrrhizic acid (GA), isolated from the roots of Glycyrrhiza glabra L., leads to a significant improvement of pharmacokinetic and pharmacodynamic parameters of drugs. Glycyrrhizic acid (GLA) is the aglycon of GA and has the same molecular skeleton. Also, GLA has own broad spectrum of biological activity. The aim of the work is to study the complexation of GLA with antimicrobial drugs to create new low-dose pharmaceutical substances. In the present study, for the first time complex compounds of GLA and antibiotic sulfanilamide (Strep) were synthesized at different ratios «host» and «guest». The composition of supramolecular complexes of GLA with Strep was identified by mass spectrometry electrospray ionization. Peaks of heterogeneous complexes consisting of monomers, dimers, trimers and tetramers of GLA with the inclusion of one molecule of Strep were registered in mass spectra. The mass spectrometric data was shown high activity of the binding Strep by GLA with formation of supramolecular complexes. Given the high biological activity of GLA and possible synergies of heterogeneous complexes, research results open up prospects to obtain new low-dose drugs of Strep.
Downloads
Metrics
References
Толстиков Г.А., Балтина Л.А., Шульц Э.Э., Покровский А.Г. Глицирризиновая кислота // Биоорганическая хи-мия. 1997. Т. 23, №9. С. 691–703.
Толстикова Т.Г., Толстиков А.Г., Толстиков Г.А. На пути к низкодозным лекарствам // Вестник Российской академии наук. 2007. Т. 77, №10. С. 867–874.
Стоник В.А., Толстиков Г.А. Природные соединения и создание отечественных лекарственных препаратов // Вестник Российской академии наук. 2008. Т. 78, №8. С. 675–684.
Толстикова Т.Г., Сорокина И.В., Брызгалов А.О., Лифшиц Г.И., Хвостов М.В. Использование подхода ком-плексообразования с глицирризиновой кислотой для создания новых кардиотропных средств // Биомедицина. 2006. Т. 1, №4. С. 115–116.
Борисенко С.Н., Лекарь А.В., Милов А.А., Ветрова Е.В., Борисенко Н.И. Масс-спектрометрия и квантовохи-мическое исследование процессов самоассоциации молекул глицирризиновой кислоты // Химия растительного сырья. 2013. №2. С. 85–92.
Borisenko S.N., Lekar A.V., Vetrova E.V., Borisenko N.I. Mass spectrometry of supramolecular complexes of glycyr-rhizic acid and benzimidazole derivatives // Chemistry of Natural Compounds. 2013. Vol. 49, N5. Рp. 969–971.
Красильникова Л.А, Авксентьева О.А., Жмурко В.В., Садовниченко Ю.А. Биохимия растений : учеб. пособие. Ростов н/д, 2004. 224 с.
Lu D., Zhang S., Li H., Dai Y. Separation of glycyrrhetic acid monoglucuronide from glycyrrhizin hydrolysates by macroporous resins // Journal of Biotechnology. 2008. Vol. 136. Pp. 472–473.
Bombardelli E., Curd S.B., Della L.R., Del N.P., Tubaro A., Gariboldi P. Anti-inflammatory activity of 18-[beta]-glycyrrhetinic acid in Phytosome form // Journal Fitoterapia. 1989. Vol. 60. Pp. 29–37.
Akao T. Effects of glycyrrhizin and glycyrrhetic acid on the growth, glycyrrhizin β-D-glucuronidase and 3β-hydroxysteroid dehydrogenase of human intestinal bacteria // Journal Biological and Pharmaceutical Bulletin. 2000. Vol. 23, Is.1. Pp. 104–107.
Farese S., Kruse A., Pasch A., Dick B., Frey B.M., Uehlinger D.E., Frey F.J. Glycyrrhetinic Acid Food Supplementation Lowers Serum Potassium Concentration in Chronic Hemodialysis Patients // Journal Kidney International. 2009. Vol. 76, Iss.8. Рp. 877–884.
Shibata S.A. Drug over the millennia: Pharmacognosy, chemistry, and pharmacology of licorice // Journal Yakugaku Zasshi. 2000. Vol. 120, Iss. 10. Pp. 849–862.
Shi J., Xiao J., Wei D. Synthesis of biotinylated 18β-glycyrrhetinic acid and its effect on tumor cells activity // Journal Medicinal Chemistry Research. 2009. Vol. 18, Pp. 538–544.
Kalaiarasi P., Kaviarasan K., Pugalendi K.V. Hypolipidemic activity of 18β-glycyrrhetinic acid on streptozotocin-induced diabetic rats // European Journal of Pharmacology. 2009. Vol. 612. Pp. 93–97.
Lekar’ A.V., Yakovishin L.A., Borisenko S.N. Vetrova E.V., Borisenko N.I. Сomplexation of antibiotic levomycetin (chloroamphenicol) with α-hederin and hederasaponin c under the conditions of electrospray // Journal of Analytical Chemistry. 2011. Vol. 66, Iss.14. Рp. 1437–1440.
Lekar' A.V., Vetrova E.V., Borisenko N.I., Yakovishin L.A., Grishkovets V.I. Mass spectrometric study on plant gly-cosides molecular complexation with streptocid (sulfanylamide) // Russian Journal of Bioorganic Chemistry. 2012. Vol. 38, Iss.7. Pp. 749–752.
Zhou X., Zhao L., Liu X., Li X., Jia F., Zhang Y., Wang Y. Antimycobacterial and synergistic effects of 18β-Glycyrrhetinic acid or glycyrrhetinic acid-30-piperazine in combination with isoniazid, rifampicin or streptomycin against mycobacterium bovis // Phytother. Res. 2012. Vol. 26. Pp. 253–258.
Борисенко С.Н., Лекарь А.В., Ветрова Е.В., Филонова О.В., Борисенко Н.И. Масс-спектрометрическое иссле-дование процессов самоассоциации молекул глицирретиновой кислоты // Химия растительного сырья. 2015. № 1. C. 89–94.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors, which are published in this journal, agree to the following conditions:
1. Authors retain the copyright to the work and transfer to the journal the right of the first publication along with the work, at the same time licensing it under the terms of the Creative Commons Attribution License, which allows others to distribute this work with the obligatory indication of the authorship of this work and a link to the original publication in this journal .
2. The authors retain the right to enter into separate, additional contractual agreements for the non-exclusive distribution of the version of the work published by this journal (for example, to place it in the university depository or to publish it in a book), with reference to the original publication in this journal.
3. Authors are allowed to post their work on the Internet (for example, in a university repository or on their personal website) before and during the review process of this journal, as this may lead to a productive discussion, as well as more links to this published work.
