BIOLOGICAL ACTIVITY OF NATURAL QUINAZOLINE ALKALOIDS
UDC 547.94:615.281.9
Abstract
To date, quinazoline alkaloids of natural origin, as well as synthetic derivatives based on them, whose structure contains an aromatic heterocyclic system including a pyrimidine cycle and a benzoin ring connected to it, are promising according to the criterion of the optimal profile of pharmacological activity. Currently, several hundred compounds of the quinazoline nature have been identified with a wide range of biological activities, including psychotropic (antidepressant, antipsychotic, sedative, hypnotic, anticonvulsant, etc.), antiplatelet, hypotensive, anti-inflammatory, antioxidant and other types of activities. It has been proven that quinazoline alkaloids have an anti-infectious effect, exhibiting antibacterial, antifungal, antiparasitic, antiviral and other effects. The alkaloids of the quinazoline and quinazolinone series were originally isolated from plant sources. Currently, sources of animal and bacterial origin are used. Interest in quinazolines and quinazolinones, as compounds with a unique chemical structure and a wide range of pharmacological action, is constantly growing. The purpose of the study is to analyze the results obtained by domestic and foreign scientists in the study of the pharmacological activity of alkaloids – derivatives of quinazoline of natural origin and compounds synthesized based on their structure, as well as to assess and predict the degree of safety of use in medical practice using data from literary sources and calculated using computer modeling methods. The paper substantiates the prospects of using alkaloids of quinazolinone derivatives not only as medicines, but also as starting compounds for the synthesis of new derivatives showing pronounced activity.
Downloads
Metrics
References
Upasani A.S., Jagdale A.S. International Journal of Molecular Sciences, 2021, vol. 5(2), pp. 6–17. https://doi.org/10.22377/ijms.v5i2.128.
Bhat M., Balagali S.L., Mamatha S.V., Sagar B.K., Sekhar E.V. Studies in Natural Products Chemistry, 2021, vol. 71, pp. 185–219. https://doi.org/10.1016/B978-0-323-91095-8.00005-2.
Long S. Synthesis and biological evaluation of indole alkaloid derivatives based on natural products. Porto, 2019, 393 p.
Wahan S.K., Sharma B., Chawla P.A. J. Heterocycl. Chem., 2022, vol. 59(2), pp. 239–257. https://doi.org/10.1002/jhet.4382.
Kshirsagar U.A. Organic & Biomolecular Chemistry, 2015, vol. 13(36), pp. 9336–9352. https://doi.org/10.1039/C5OB01379H.
Mao Z.Y., Geng H., Zhang T.T., Ruan Yu.P., Ye J.L., Huang P.Q. Organic Chemistry Frontiers, 2016, vol. 3(1), pp. 24–37. https://doi.org/10.1039/C5QO00298B.
Faisal S., Badshah S.L., Kubra B., Emwas A.H., Jaremko M. Natural Products and Bioprospecting, 2023, vol. 13(1), p. 4. https://doi.org/10.1007/s13659-022-00366-9.
Xu W.F., Chao R., Hai Yu., Guo Ya.Ya., Wei M.Ya., Wang C.Yu., Shao C.L. Journal of Natural Products, 2021, vol. 84(4), pp. 1353–1358. https://doi.org/10.1021/acs.jnatprod.1c00098.
Ames B.D., Liu H., Walsh C.T. Biochemistry, 2010, vol. 49(39), pp. 8564–8576. https://doi.org/10.1021/bi1012029.
Zhang H.W., Ying C., Tang Yi.F. Chemistry & Biodiversity, 2014, vol. 11(1), pp. 85–91. https://doi.org/10.1002/cbdv.201300220.
Umer S.M., Solangi M., Khan K.M., Saleem R.S.S. Molecules, 2022, vol. 27(21), 7586. https://doi.org/10.3390/molecules27217586
Wang Ju., He W., Huang X., Tian X., Liao S., Yang B., Wang F., Zhou X., Liu Yu. Journal of Agricultural and Food Chemistry, 2016, vol. 64(14), pp. 2910–2916. https://doi.org/10.1021/acs.jafc.6b00527.
Cheng Z., Liu D., Cheng W., Proksch P., Lin W. RSC Advances, 2018, vol. 8(55), pp. 31427–31439. https://doi.org/10.1039/C8RA06854B.
Youssef F.S., Alshammari E., Ashour M.L. International Journal of Molecular Sciences, 2021, vol. 22(4), 1866. https://doi.org/10.3390/ijms22041866.
Limbardi S., Luo X., Lin X., Liao S., Wang J., Zhou X., Yang B., Liu Yu. Molecules, 2018, vol. 23(9), 2379. https://doi.org/10.3390/molecules23092379.
Shang X.F., Morris-Natschke S.L., Yang G.Z., Liu Y.Q., Guo X., Xu X.S., Goto M., Li J.C., Zhang J.Y., Lee K.H. Medicinal Research Reviews, 2018, vol. 38(5), pp. 1614–1660. https://doi.org/10.1002/med.21492.
Lee F., Peifer K., Janussen D., Tasdemir D. Marine Drugs, 2019, vol. 17(8), 439. https://doi.org/10.3390/md17080439.
Utkina N.K. Vestnik Dal'nevostochnogo otdeleniya Rossiyskoy akademii nauk, 2004, vol. 3, pp. 66–75. (in Russ.).
Popov A.M. Biofarmatsevticheskiy zhurnal, 2012, vol. 4, no. 4, pp. 3–26. (in Russ.).
Rauscher A.A., Gyimesi M., Kovács M., Málnási-Csizmadia A. Trends in Biochemical Sciences, 2018, vol. 43(9), pp. 700–713. https://doi.org/10.1016/j.tibs.2018.06.006.
Hughes C.C., MacMillan J.B., Gaudêncio S.P., Fenical W., La Clair J.J. Angewandte Chemie International Edition, 2009, vol. 48(4), pp. 728–732. https://doi.org/10.1002/anie.200804107.
Baier A., Szyszka R. Biomolecules, 2020, vol. 10(11), 1546. https://doi.org/10.3390/biom10111546.
Shang X.F., Morris-Natschke S.L., Liu Y.Q., Li X.H., Zhang J.Y., Lee K.H. Alkaloids: Chemistry and Biology, 2022, vol. 88, pp. 1–47. https://doi.org/10.1016/bs.alkal.2021.08.002.
Nepali K., Sharma S., Ojha R., Dhar K.L. Medicinal Chemistry Research, 2013, vol. 22(1), pp. 1–15. https://doi.org/10.1007/s00044-012-0002-5.
Bhanukiran K., Singh R., Gajendra T.A., Ramakrishna K., Singh S.K., Krishnamurthy S., Kumar A., Hemalatha S. Phytomed Plus, 2023, vol. 3(2), 100439. https://doi.org/10.1016/j.phyplu.2023.100439.
Ghanta Р., Doble M., Ramaiah B. Journal of Biomolecular Structure and Dynamics, 2022, vol. 40(16), pp. 7245–7255. https://doi.org/10.1080/07391102.2021.1895887.
Zhang S.S., Tan Q.W., Guan L.P. Mini-Reviews in Medical Chemistry, 2021, vol. 21(16), pp. 2261–2275. https://doi.org/10.2174/1389557521666210111145011.
Sutare M.S., Kareppa B.M. International Journal of Life Sciences, 2020, vol. A14, pp. 55–58.
Jiang T., Zhang L., Ding M., Li M. Drug design, development and therapy, 2019, vol. 13, pp. 3773–3784. https://doi.org/10.2147/DDDT.S220396.
Zhang Y., Du W., Zhu D., Li M., Qu L., Rao G., Lin Y., Tong X., Sun Y., Huang F. The Journal of Clinical Immu-nology, 2022, vol. 244, 109102. https://doi.org/10.1016/j.clim.2022.109102.
Sharmila C.M., Devi R.C., Sureka A., MuthuKumar N.J., Banumathi V. Asian journal of pharmacy and pharmacolo-gy, 2019, vol. 5(3), pp. 518–524. https://doi.org/10.31024/ajpp.2019.5.3.13.
Shan C., Yan J.W., Wang Y.Q., Che T., Huang Z.L., Chen A.C., Yao P.F., Tan J.H., Ding Li D., Ou T.M., Gu L.Q., Huang Z.S. Journal of Medicinal Chemistry, 2017, vol. 60(4), pp. 1292–1308. https://doi.org/10.1021/acs.jmedchem.6b01218.
Du K., Ma W., Yang C., Zhou Z., Hu S., Tian Ya., Zhang H., Ma Yu, Jiang X., Zhu H., Liu H., Chen P., Liu Yu. Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, vol. 37(1), pp. 1212–1226. https://doi.org/10.1080/14756366.2022.2065672.
Liang J.L., Cha H.C., Jang Y. Molecules, 2011, vol. 16(6), pp. 4861–4883. https://doi.org/10.3390/molecules16064861.
Dallavalle S., Merlini L., Beretta G.L., Tinelli S., Zunino F. Bioorganic & Medicinal Chemistry, 2004, vol. 14(23), pp. 5757–5761. https://doi.org/10.1016/j.bmcl.2004.09.039.
Nacro K., Zha C.S., Guzzo P.R., Herr R.J., Peace D., Friedrich T.D. Bioorganic & Medicinal Chemistry, 2007, vol. 15(12), pp. 4237–4246. https://doi.org/10.1016/j.bmc.2007.03.067.
Pines M., Spector I. Molecules, 2015, vol. 20(1), pp. 573–594. https://doi.org/10.3390/molecules20010573.
Mishra V.K., Mishra M., Mishra S., Sahu P., Kashaw S.K. Asian journal of pharmacy and pharmacology, 2015, vol. 1(1), pp. 10–15.
Cao D.H., Liao S.G., Sun P., Xiao Yi D., Xiao C.F., Hu H.B., Weckwerth W., Xu Yo K. Phytochemistry, 2020, vol. 177, 112449. https://doi.org/10.1016/j.phytochem.2020.112449.
Jiang S., Zeng Q., Gettayacamin M., Tungtaeng A., Wannaying S., Lim A., Hansukjariya P., Okunji C.O., Zhu S., Fang D. Antimicrob Agents Chemother, 2005, vol. 49(3), pp. 1169–1176. https://doi.org/10.1128/aac.49.3.1169-1176.2005.
Keller T.L., Zocco D., Sundrud M.S., Hendrick M., Edenius M., Yum J., Kim Y.J., Lee H.K., Cortese J.F., Wirth D.F., Dignam J.D., Rao A., Yeo C.Y., Mazitschek R., Whitman M. Nature Chemical Biology, 2012, vol. 8(3), pp. 311–317. https://doi.org/10.1038/nchembio.790.
McLaughlin N.P., Evans P., Pines M. Bioorganic & Medicinal Chemistry, 2014, vol. 22(7), pp. 1993–2004. https://doi.org/10.1016/j.bmc.2014.02.040.
Hou X., Zhou J., Yang R., Liu Sh., Bi M., Liu T., Fan Ch., Guan H., Teng W., Shan Z., Li Y. Endocr Metab Immune Disord. Drug Targets, 2017, vol. 17(2), pp. 141–148. https://doi.org/10.2174/1871530317666170424101256.
Wang J., Wang B., Lv X., Wang Y. International Journal of Immunopathology and Pharmacology, 2020, vol. 34. https://doi.org/10.1177/2058738420974893.
Zhao Z., He X., Han W., Chen X., Liu P., Zhao X., Wang X., Zhang L., Wu S., Zheng X. Journal of Ethnopharma-cology, 2019, vol. 231, pp. 337–354. https://doi.org/10.1016/j.jep.2018.11.035.
Na M.W., Jeong S.Y., Ko Y.J., Kang D.M., Pang C., Ahn M.J., Kim K.H. ACS Omega, 2022, vol. 7(27), pp. 23736–23743. https://doi.org/10.1021/acsomega.2c02380.
Tian K.M., Li J.J., Xu S.W. Pharmacological Research, 2019, vol. 141, pp. 541–550. https://doi.org/10.1016/j.phrs.2018.12.019.
Lee S.H., Song J.K., Jeong B.S., Jeong T.C., Chang H.W., Lee E.S., Jang Y. Molecules, 2008, vol. 13(2), pp. 272–300. https://doi.org/10.3390/molecules13020272.
Son J.K., Chang H.W., Jahng Y. Molecules, 2015, vol. 20(6), pp. 10800–10821. https://doi.org/10.3390/molecules200610800.
Fatima M., Iqubal M.K., Iqubal A., Kaur H., Gilani S.J., Rahman M.H., Ahmadi A., Rizwanullah. Anti-Cancer agents in medicinal chemistry, 2022, vol. 22(4), pp. 668–686. https://doi.org/10.2174/1871520621666210708123750.
Galagudza M.M., Bel'skiy Yu.P., Bel'skaya N.V. Sibirskiy zhurnal klinicheskoy i eksperimental'noy meditsiny. 2023, vol. 38, no. 1, pp. 13–20. https://doi.org/10.29001/2073-8552-2023-38-1-13-20. (in Russ.).
Yu H., Jin H., Gong W., Wang Z., Liang H. Molecules, 2013, vol. 18(2), pp. 1826–1843. https://doi.org/10.3390/molecules18021826.
Sun Q., Xie L., Song J., Li X. Journal of Ethnopharmacology, 2020, vol. 262. 113164. https://doi.org/10.1016/j.jep.2020.113164.
Popov A.M., Osipov A.N., Korepanova Ye.A., Krivoshapko O.N., Shtoda Yu.P., Klimovich A.A. Biofizika, 2015, vol. 60, no. 4, pp. 700–707. (in Russ.).
Shang X.F., Morris-Natschke S.L., Yang G.Z., Liu Y.Q., Guo X., Xu X.S., Goto M., Li J.C., Zhang J.Y., Lee K.H. Medicinal Research Reviews, 2018, vol. 38(5), pp. 1614–1660. https://doi.org/10.1002/med.21492.
Jahng Y. Archives of Pharmaceutical Research, 2013, vol. 36(5), pp. 517–535. https://doi.org/10.1007/s12272-013-0091-9.
Clevenger K.D., Ye R., Bok J.W., Thomas P.M., Islam M.N., Miley G.P., Robey M.T., Chen C., Yang K.H., Swyers M., Wu E., Gao P., Wu C.C., Keller N.P., Kelleher N.L. Biochemistry, 2018, vol. 57(23), pp. 3237–3243. https://doi.org/10.1021/acs.biochem.8b00076.
Chao R., Wu YuW., Lu L., Xu W.F., Wang C.Yu., Shao C.L. Chemistry of Natural Compounds, 2021, vol. 57, pp. 343–345. https://doi.org/10.1007/s10600-021-03347-5.
Del V., Martinez A.L., Figueroa M., Raja H.A., Mata R. Planta Medica, 2016, vol. 82(14), pp. 1286–1294. https://doi.org/10.1055/s-0042-111393.
Süssmuth R.D., Mainz A. Angewandte Chemie International Edition, 2017, vol. 56(14), pp. 3770–3821. https://doi.org/10.1002/anie.201609079.
He D., Wang M., Zhao S., Shu Y., Zeng H., Xiao C., Lu C., Liu Y. Fitoterapia, 2017, vol. 119, pp. 136–149. https://doi.org/10.1016/j.fitote.2017.05.001.
Zhang D., Yang X., Kang J.S., Choi H.D., Son B.W. Journal of Antibiotics, 2008, vol. 61(1), pp. 40–42. https://doi.org/10.1038/ja.2008.108.
Orlova T.I., Bulgakova V.G., Polin A.N. Antibiotics and chemotherapy, 2017, vol. 62, no. 5-6, pp. 68–76. (in Russ.).
Zhang C., Hu L., Liu D., Huang J., Lin W. Frontiers in Pharmacology, 2020, vol. 11, 760. https://doi.org/10.3389/fphar.2020.00760.
Youssef F.S., Simal-Gandara J. Biomedicines, 2021, vol. 9(5), 485. https://doi.org/10.3390/biomedicines9050485.
Quang T.H., Anh L.N., Hanh T.T.H., Cuong N.X., Ngan N.T.T., Trung N.Q., Nam N.H. Vietnam Journal of Chemis-try, 2021, vol. 59(5), pp. 660–666. https://doi.org/10.1002/vjch.202100032.
Dai J.R., Carté B.K., Sidebottom P.J., Sek Yew A.L.S., Ng S.B., Huang Y., Butler M.S. Journal of Natural Products, 2001, vol. 64(1), pp. 125–126. https://doi.org/10.1021/np000381u.
Hidayatullah A., Putra W.E., Sustiprijatno, Heikal M.F., Widiastuti D., Permatasari G.W., Faradilla D.M. Science & Technology Asia, 2023, vol. 28(1), pp. 190–205. https://doi.org/10.14456/scitechasia.2023.16.
Salem M., El-Metwally M., Saber W., Negm S., El-Kott A., Mazroua Y., Makhlouf A., Moustafa M. Biology Science and Education, 2022, vol. 46(8), pp. 1979–1988. https://doi.org/10.32604/biocell.2022.019301.
Rezende D.I.S.P., Boonpothong Р., Sousa E., Kijjoa A., Pinto M.M.M. Natural Product Reports journal, 2019, vol. 36(1), pp. 7–34. https://doi.org/10.1039/C8NP00043C.
Qian S.Y., Yang C.L., Khan A., Chen R.X., Wu M.S., Tuo L., Wang Q., Liu J.G., Cheng G.G. Natural Product Re-search, 2019, vol. 33(9), pp. 1387–1391. https://doi.org/10.1080/14786419.2018.1475381.
Voskoboynik O.Y., Kolomoets O.S., Kovalenko S.I. et al. Chemistry of Heterocyclic Compounds, 2017, vol. 53, no. 8, pp. 892–904. https://doi.org/10.1007/s10593-017-2142-5.
Matsuura H.N., Fett-Not that A.G. Plant toxins, 2015, vol. 2(7), pp. 1–15. https://doi.org/10.1007/978-94-007-6728-7_2-1.
Gorlenko S.L., Kiselev G.Yu., Budanova E.V., Zamyatnin Jr.A.A, Ikryannikova L.N. Antibiotics, 2020, vol. 9(4), 170. https://doi.org/10.3390/antibiotics9040170.
Kirschning A., Taft F., Knobloch T. Organic and Biomolecular Chemistry, 2007, vol. 5(20), pp. 3245–3259.
Kalgutkar A.S., Sogliya D.R. Expert Opinion on Drug Metabolism and Toxicology, 2005, vol. 1(1), pp. 91–142. https://doi.org/10.1517/17425255.1.1.91.
Kryshen' K.L., Katel'nikova A.Ye., Muzhikyan A.A., Makarova M.N., Makarov V.G. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya, 2018, vol. 8, no. 1, pp. 44–55. https://doi.org/10.30895/1991-2919-2018-8-1-44-55. (in Russ.).
Liman K., Nutsa D.K., Kiritse K., Negrash S., Arsen A.L., Gumen M., Sarigiannis D.A. Toxicological Reports, 2018, vol. 5, pp. 943–953. https://doi.org/10.1016/j.toxrep.2018.08.017.
Zefirova O.N., Zefirov N.S. Vestnik Moskovskogo universiteta. Seriya 2. Khimiya, 2002, vol. 43, no. 4, pp. 251–256. (in Russ.).
Stepan A.F., Walker D., Bauman J., Price D.A, Bailey T.A., Kalgatkar A.S., Leo M.D. Chemical Research in Toxicol-ogy, 2011, vol. 24(9), pp. 1345–1410. https://doi.org/10.1021/tx200168d.
Sarymzakova R.K., Abdurashitova Yu.A., Dzhamanbayev Zh.A. Vestnik Moskovskogo universiteta. Seriya 2. Khimiya, 2006, vol. 47, no. 3, pp. 242–244. (in Russ.).
Xiao Z., Morris-On a Wheelbarrow S.L., Li K.H. Medical Research Reviews, 2016, vol. 36(1), pp. 32–91. https://doi.org/10.1002/med.21377.
Drwal M.N., Banerjee P., Dunkel M., Wettig M.R., Preissner R. Nucleic acids research, 2014, vol. 42(W1), pp. W53–W58. https://doi.org/10.1093/nar/gku401.
Copyright (c) 2025 chemistry of plant raw material

This work is licensed under a Creative Commons Attribution 4.0 International License.

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.







