vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8331-2020-56-2-187-191vestich-582Research ArticleОРГАНИЧЕСКАЯ ХИМИЯORGANIC CHEMISTRYСинтез изоксазольных и изотиазольных производных куркуминаSynthesis of isoxazole and isothiazole derivatives of curcuminАкишинаЕ. А.AkishinaE. A.

Акишина Екатерина Александровна – аспирант, мл. науч. сотрудник

ул. Сурганова, 13, 220072, Минск

Ekaterina A. Akishina – Graduate student, Junior Researcher

13, Surganov Str., 220072, Minsk

akishinaea@ifoch.bas-net.byДикусарЕ. А.DikusarE. A.

Дикусар Евгений Анатольевич – канд. хим. наук, ст. науч. сотрудник

ул. Сурганова, 13, 220072, Минск

Evgenij A. Dikusar – Ph. D. (Chemistry), Senior Researcher

13, Surganov Str., 220072, Minsk

dikusar@ifoch.bas-net.byПеткевичС. К.PetkevichS. K.

Петкевич Сергей Константинович – канд. хим. наук, вед. науч. сотрудник

ул. Сурганова, 13, 220072, Минск

Sergey K. Petkevich – Ph. D. (Chemistry), Leading Researcher

13, Surganov Str., 220072, Minsk

petkevich@ifoch.bas-net.byПоткинВ. И.PotkinV. I.

Поткин Владимир Иванович – член-корреспондент, д-р хим. наук, профессор, зав. отделом

ул. Сурганова, 13, 220072, Минск

Vladimir I. Potkin – Corresponding Member, D. Sc. (Chemistry), Professor, Head of the Department

13, Surganov Str., 220072, Minsk

potkin@ifoch.bas-net.byИнститут физико-органической химии Национальной академии наук БеларусиInstitute of Physical Organic Chemistry of the National Academy of Sciences of Belarus202006062020562187191Copyright © Акишина Е.А., Дикусар Е.А., Петкевич С.К., Поткин В.И., 20202020Акишина Е.А., Дикусар Е.А., Петкевич С.К., Поткин В.И.Akishina E.A., Dikusar E.A., Petkevich S.K., Potkin V.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/582

Куркумин – химическое соединение, содержащееся в клубневидных корневищах растения куркума и обладающее антиоксидантными свойствами, а также оказывающее сильное противовоспалительное, противовирусное, болеутоляющее, антимикробное и противоопухолевое действия. Производные куркумина интенсивно исследуются в качестве потенциальных лекарственных средств – противоопухолевых препаратов для терапии некоторых форм онкологических заболеваний. Благодаря присутствию в его молекуле реакционноспособных функциональных групп может служить удобным и легкодоступным исходным соединением для последующей химической модификации. Описан синтез сложных эфиров куркумина и 5-фенилизоксазол-3-карбоновой, 5-(р-толил)изоксазол-3-карбоновой, 4,5-дихлоризотиазол-3-карбоновой кислот и аддукта 5-(р-толил)изоксазол-3-карбальдегида с куркумином. Сложные эфиры получали ацилированием куркумина хлорангидридами гетероциклосодержащих карбоновых кислот в среде диэтилового эфира в присутствии триэтиламина. Приведены ИК- и ЯМР-спектры полученных соединений.

Curcumin is a chemical compound with antioxidant properties as well as strong anti-inflammatory, antiviral, analgesic, antimicrobial and antitumor effect, contained in the tuberous rhizomes of the turmeric plant (Curcuma longa). Curcumin derivatives are being intensively studied as potential drugs – antitumor drugs for the treatment of certain forms of cancer. The presence of reactive functional groups makes curcumin a convenient starting compound for the further chemical modification. The esters of curcumin and 5-phenylisoxazole-3-carboxylic acid, 5-(p-tolyl)isoxazole-3-carboxylic acid, 4,5- dichloroisothiazole-3-carboxylic acid and adduct of 5-(p-tolyl)isoxazol-3-carbaldehyde with curcumin were synthesized. Esters were obtained by acylation of curcumin with heterocycle-containing carboxylic acid chloride in diethyl ether in the presence of triethylamine. The IR and NMR spectra of the obtained compounds are described.

куркуминсложные эфирыизоксазолизотиазолконденсацияацилированиеаддуктcurcuminestersisoxazoleisothiazolecondensationacylationadductReferencesXu, P. Curcumin protects rat heart mitochondria against anoxia-reoxygenation induced oxidative injury / P. Xu [et al.] // Canadian Journal of Physiology and Pharmacology. – 2013. – Vol. 91, N 9. – P. 715–723. https://doi.org/10.1139/cjpp-2013-0055Xu P., Yao Y., Guo P., Wang T., Yang B., Zhang Z. Curcumin protects rat heart mitochondria against anoxia-reoxygenation induced oxidative injury. Canadian Journal of Physiology and Pharmacology, 2013, vol. 91, no. 9, pp. 715–723. https://doi.org/10.1139/cjpp-2013-0055Menon, V. P. Antioxidant and anti-inflammatory properties of curcumin / V. P. Menon, A. R. Sudheer // Advances in experimental medicine and biology. – 2007. – Vol. 595. – P. 105–125. https://doi.org/10.1007/978-0-387-46401-5_3Menon V. P., Sudheer A. R. Antioxidant and anti-inflammatory properties of curcumin. Advances in experimental medicine and biology, 2007, vol. 595, pp. 105–125. https://doi.org/10.1007/978-0-387-46401-5_3Alsamydai, A. Pharmacological aspects of curcumin: review article / A. Alsamydai, N. Jaber // International Journal of Pharmacognosy. – 2018. – Vol. 5, N 6. – P. 313–326. https://doi.org/10.13040/IJPSR.0975-8232.IJP.5(6).313-26Alsamydai A., Jaber N. Pharmacological aspects of curcumin: review article. International Journal of Pharmacognosy, 2018, vol. 56, no. 6, pp. 313–326. https://doi.org/10.13040/IJPSR.0975-8232.IJP.5(6).313-26Gul, P. Antimicrobial activity of turmeric extract and its potential use in food industry / P. Gul, J. Bakht // Journal of Food Science and Technology. – 2015. – Vol. 52. – P. 2272–2279. https://doi.org/10.1007/s13197-013-1195-4Gul P., Bakht J. Antimicrobial activity of turmeric extract and its potential use in food industry. Journal of Food Science and Technology, 2015, vol. 52, pp. 2272–2279. https://doi.org/10.1007/s13197-013-1195-4Said, S. A.-A. Prevention of sodiumvalproate-induced hepatotoxicity by curcumin, rosiglitazone and N-acetylcysteine in rats / S. A.-A. Said, D. S. El-Agamy // Arzneimittelforschung. – 2010. – Vol. 60, N 11. – P. 647–653. https://doi.org/10.1055/s-0031-1296342Said S. A.-A., El-Agamy D. S. Prevention of sodiumvalproate-induced hepatotoxicity by curcumin, rosiglitazone and N-acetylcysteine in rats. Arzneimittelforschung, 2010, vol. 60, no. 11, pp. 647–653. https://doi.org/10.1055/s-0031-1296342Cridge, B. J. Curcumin and its derivatives in breast cancer: Current developments and potential for the treatment of drug-resistant cancers / B. J. Cridge, L. Larsen, R. J. Rosengren // Oncology Discovery. – 2013. – Vol. 1, N 6. – P. 1–9. https://doi.org/10.7243/2052-6199-1-6Cridge B. J., Larsen L., Rosengren R. J. Curcumin and its derivatives in breast cancer: Current developments and potential for the treatment of drug-resistant cancers. Oncology Discovery, 2013, vol. 1, no. 6, pp. 1–9. https://doi.org/10.7243/2052-6199-1-6Identification of 4-Arylidene Curcumin Analogues as Novel Proteasome Inhibitors for Potential Anticancer Agents Targeting 19S Regulatory Particle Associated Deubiquitinase / X. Yue [et al.] // Biochemical Pharmacology. – 2017. – Vol. 137. – P. 29–50. https://doi.org/10.1016/j.bcp.2017.04.032Yue X., Zuo Y., Ke H., Luo J., Lou L., Qin W., Wang Y., Liu Z., Chen D., Sun H., Zheng W., Zhu C., Wang R., Wen G., Du J., Zhou B., Bu X. Identification of 4-Arylidene Curcumin Analogues as Novel Proteasome Inhibitors for Potential Anticancer Agents Targeting 19S Regulatory Particle Associated Deubiquitinase. Biochemical Pharmacology, 2017, vol. 137, pp. 29–50. https://doi.org/10.1016/j.bcp.2017.04.032Mbese, Z. Curcumin and Its Derivatives as Potential Therapeutic Agents in Prostate, Colon and Breast Cancers / Z. Mbese, V. Khwaza, B. A. Aderibigbe // Molecules. – 2019. – Vol. 24, N 23. – P. 4386. https://doi.org/10.3390/molecules24234386Mbese Z., Khwaza V., Aderibigbe B. A. Curcumin and Its Derivatives as Potential Therapeutic Agents in Prostate, Colon and Breast Cancers. Molecules, 2019, vol. 24, no. 23, pp. 4386. https://doi.org/10.3390/molecules24234386Effects of Stable Degradation Products of Curcumin on Cancer Cell Proliferation and Inflammation / K. Z. Sanidad [et al.] // Journal of Agricultural and Food Chemistry. – 2016. – Vol. 64, N 2. – P. 9189–9195. https://doi.org/10.1021/acs.jafc.6b04343Sanidad K. Z., Zhu J., Wang W., Du Z., Zhang G. Effects of Stable Degradation Products of Curcumin on Cancer Cell Proliferation and Inflammation. Journal of Agricultural and Food Chemistry, 2016, vol. 64, no. 2, pp. 9189–9195. https://doi.org/10.1021/acs.jafc.6b04343Multicomponent synthesis of new curcumin-based pyrano[2,3-d]pyrimidine derivatives using a nano-magnetic solid acid catalyst / F. Panahi // New Journal of Chemistry. – 2017. – Vol. 41, N 20. – P. 12293–12302. https://doi.org/10.1039/C7NJ02370GPanahi F., Niknam E., Sarikhani S., Haghighi F., Khalafi-Nezhada A. Multicomponent synthesis of new curcuminbased pyrano[2,3-d]pyrimidine derivatives using a nano-magnetic solid acid catalyst. New Journal of Chemistry, 2017, vol. 41, no. 20, pp. 12293–12302. https://doi.org/10.1039/C7NJ02370GSynthesis and Biological Evaluation of Curcumin Derivatives Containing NSAIDs for Their Anti-inflammatory Activity / W. Liu [et al.] // Bioorganic & Medicinal Chemistry Letters. – 2015. – Vol. 25, N 15. – P. 3044–3051. https://doi.org/10.1016/j.bmcl.2015.04.077Liu W., Li Y., Yue Y., Zhang K., Chen Q., Wang H., Lu Y., Huang M., Zheng X., Du Z. Synthesis and Biological Evaluation of Curcumin Derivatives Containing NSAIDs for Their Anti-inflammatory Activity. Bioorganic & Medicinal Chemistry Letters, 2015, vol. 25, no. 15, pp. 3044–3051. https://doi.org/10.1016/j.bmcl.2015.04.077Synthesis of innovative biochemical active mixed ligand metal(II) complexes with thiazole containing Schiff base: In vitro antimicrobial profile / N. Raman [et al.] // Applied Organometallic Chemistry. – 2017. – Vol. 32, N 1. – P. 1–13. https://doi.org/10.1002/aoc.3922Raman N., Chandrasekar T., Kumaravel G., Mitu L. Synthesis of innovative biochemical active mixed ligand metal(II) complexes with thiazole containing Schiff base: In vitro antimicrobial profile. Applied Organometallic Chemistry, 2017, vol. 32, no. 1, pp. 1–13. https://doi.org/10.1002/aoc.3922Herbo-mineral based Schiff base ligand and its metal complexes: Synthesis, characterization, catalytic potential and biological applications / A. Kareem [et al.] // Journal of Photochemistry and Photobiology B: Biology. – 2016. – Vol. 160. – P. 163–171. https://doi.org/10.1016/j.jphotobiol.2016.03.030Kareem A., Laxmi, Arshad M., Nami S. A. A., Nishat N. Herbo-mineral based Schiff base ligand and its metal complexes: Synthesis, characterization, catalytic potential and biological applications. Journal of Photochemistry and Photobiology B: Biology, 2016, vol. 160, pp. 163–171. https://doi.org/10.1016/j.jphotobiol.2016.03.030Дикусар, Е. А. Простые и сложные эфиры в линкерных технологиях. Современные аспекты молекулярного дизайна – от душистых веществ до биологически активных соединений / Е. А. Дикусар. – Saarbrücken, Deutschland: LAP LAMBERT Academic Publishing, 2014. – 582 с.Dikusar E. A. Ethers and esters in linker technologies. Modern aspects of molecular design – from fragrant substances to biologically active compounds. Saarbrücken, Deutschland: LAP LAMBERT Academi, 2014. 582 p. (in Russian).Polarization, excited states, trans-cis properties and anisotropy of thermal and electrical conductivity of the 4- (phenyldiazenyl)aniline in PVA matrix / S. Shahab [et al.] // Journal of Molecular Structure. – 2017. – Vol. 1141. – P. 703–709. https://doi.org/10.1016/j.molstruc.2017.04.014Shahab S., Filippovich L., Sheikhi M., Kumar R., Dikusar E., Yahyaei H., Muravsky A. Polarization, excited states, trans-cis properties and anisotropy of thermal and electrical conductivity of the 4-(phenyldiazenyl)aniline in PVA matrix. Journal of Molecular Structure, 2017, vol. 1141, pp. 703–709. https://doi.org/10.1016/j.molstruc.2017.04.014

The authors declare that there are no conflicts of interest present.