oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2025-24-5-163-170oncotomsk-3867Research ArticleОБЗОРЫREVIEWSТрополон и его производные: структура, синтез, применение в медицине (обзор)Tropolone and its derivatives: structure, synthesis, application in medicine (review)https://orcid.org/0000-0003-3753-4463ХодаковаД. В.KhodakovaD. V.

Ходакова Дарья Владиславовна - научный сотрудник испытательного лабораторного центра

SPIN-код: 8718-3983

Researcher ID (WOS): MCK-3167-2025

Author ID (Scopus): 57221463056

344037, Ростов-на-Дону, ул. 14 линия, 63

Darya V. Khodakova - Researcher, Testing Laboratory Center

Researcher ID (WOS): MCK-3167-2025

Author ID (Scopus): 57221463056

63, 14th Line St., Rostov-on-Don, 344037

KhodakovaDV@yandex.ruhttps://orcid.org/0000-0003-0676-0871ГончароваА. С.GoncharovaA. S.

Гончарова Анна Сергеевна - кандидат биологических наук, заведующая испытательным лабораторным центром

SPIN-код: 7512-2039

Author ID (Scopus): 57215862139

344037, Ростов-на-Дону, ул. 14 линия, 63

Anna S. Goncharova - PhD, Head of the Testing Laboratory Center

Author ID (Scopus): 57215862139

63, 14th Line St., Rostov-on-Don, 344037

https://orcid.org/0000-0001-7823-3865ГалинаА. В.GalinaA. V.

Галина Анастасия Владимировна - младший научный сотрудник испытательного лабораторного центра.

344037, Ростов-на-Дону, ул. 14 линия, 63

Anastasia V. Galina - Junior Researcher, Testing Laboratory Center

Author ID (Scopus): 57221460594

63, 14th Line St., Rostov-on-Don, 344037

https://orcid.org/0000-0002-9747-8515ГуроваС. В.GurovaS. V.

Гурова Софья Валерьевна - младший научный сотрудник испытательного лабораторного центра.

344037, Ростов-на-Дону, ул. 14 линия, 63

Sofia V. Gurova - Junior Researcher, Testing Laboratory Center.

63, 14th Line St., Rostov-on-Don, 344037

https://orcid.org/0000-0003-3011-6904ГоловиновИ. В.GolovinovI. V.

Головинов Игорь Викторович - младший научный сотрудник испытательного лабораторного центра.

344037, Ростов-на-Дону, ул. 14 линия, 63

Igor V. Golovinov - Junior Researcher, Testing Laboratory Center.

63, 14th Line St., Rostov-on-Don, 344037

https://orcid.org/0009-0006-1125-2897ШульгаА. А.ShulgaA. A.

Шульга Анна Александровна - младший научный сотрудник испытательного лабораторного центра.

344037, Ростов-на-Дону, ул. 14 линия, 63

Anna A. Shulga - Junior Researcher, Testing Laboratory Center.

63, 14th Line St., Rostov-on-Don, 344037

https://orcid.org/0009-0004-7432-9420КамлыкД. В.KamlykD. V.

Камлык Дмитрий Вячеславович - аспирант отделения абдоминальной онкологии № 1.

344037, Ростов-на-Дону, ул. 14 линия, 63

Dmitry V. Kamlyk - Postgraduate, Department of Abdominal Oncology No. 1.

63, 14th Line St., Rostov-on-Don, 344037

ФГБУ «Национальный медицинский исследовательский центр онкологии» Минздрава РоссииРоссияNational Medical Research Centre for Oncology, Ministry of Health RussiaRussian Federation202520112025245163170Copyright © Ходакова Д.В., Гончарова А.С., Галина А.В., Гурова С.В., Головинов И.В., Шульга А.А., Камлык Д.В., 20252025Ходакова Д.В., Гончарова А.С., Галина А.В., Гурова С.В., Головинов И.В., Шульга А.А., Камлык Д.В.Khodakova D.V., Goncharova A.S., Galina A.V., Gurova S.V., Golovinov I.V., Shulga A.A., Kamlyk D.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/3867Актуальность

Актуальность. Трополоны и его производные принадлежат к семейству природных продуктов, содержащих трополоноидный мотив (уникальный циклогепта-2,4,6-триеноновый фрагмент), который представляет собой семичленное небензоидное ароматическое кольцо. С развитием органической химии было открыто и синтезировано большое количество новых соединений трополонового ряда. За последние 10 лет было опубликовано свыше 350 исследований, в которых использовались данные вещества.

Цель исследования – обобщение опубликованных данных о структуре, методах синтеза и применении в разных областях медицины соединений трополонового ряда.

Материал и методы

Материал и методы. Проведен поиск литературы с использованием баз данных PubMed, eLibrary и Google Scholar по ключевым словам «tropolones», «chemical structure of tropolones», «synthesis of tropolones», «biological activity of tropolones». Из отобранных для изучения 535 источников литературы подробно было проанализировано 39 публикаций. В представленном обзоре рассматриваются результаты исследований за период с 1936 по 2024 г.

Результаты

Результаты. Рассматриваются структура широко распространенных трополонов и вопрос о химическом синтезе трополонов различными методами из шестии семичленных углеродных колец посредством реакций циклизации и циклоприсоединения, а также получение новых соединений при помощи конденсации трополона с другими функциональными группами. Результаты современных исследований, выполненных на культурах опухолевых клеток, различных видах бактерий и лабораторных животных, демонстрируют, что представители соединений трополонового ряда обладают широким спектром биологических эффектов, что делает их перспективными ведущими молекулами для разработки различных лекарственных средств. Трополоны проявляют свои свойства преимущественно посредством координации катионов в активных центрах металлоферментов. Авторы в своих работах предлагают различные пути и мишени их действия.

Заключение

Заключение. Трополоны обладают широким спектром биологической активности, включая противовирусную, противомикробную и противоопухолевую. Исследование зависимости «структура – активность» и накопление информации о химико-физических свойствах полученных веществ привели к разработке более эффективных методов синтеза и получению соединений трополонового ряда с улучшенной эффективностью и селективностью, что подтверждается в исследованиях как in vitro, так и in vivo. Однако точные механизм(ы) действия трополонов остаются неизвестными, поэтому требуются дальнейшие исследования в этом направлении.

Introduction

Introduction. Tropolones and their derivatives are members of a family of natural products containing a tropolonoid motif, a unique cyclohepta-2,4,6-trienone fragment, which constitutes a seven-membered nonbenzenoid aromatic ring. Following the advent of organic chemistry, a substantial number of novel tropolone derivatives have been synthesized and identified. In the past decade, the number of publications employing these substances has exceeded 350. the objective of the present review was to provide a concise summary of the extant published data concerning the structural characteristics, methods of synthesis, and applications in various medical disciplines of tropolone series compounds.

Material and Methods

Material and Methods. A comprehensive literature search was conducted using the PubMed, eLibrary, and Google Scholar databases. The search was conducted using the keywords “tropolone,” “chemical structure of tropolones,” “synthesis of tropolones,” and “biological activity of tropolones”. Of the 535 literature sources that were selected for study, 39 publications were analyzed in detail. The review includes studies from 1936 to 2024.

Results

Results. The structural characterization of tropolones, the chemical synthesis of tropolones through diverse methodologies involving sixand seven-membered carbon rings, and the cyclization and cycloaddition reactions, are addressed. Additionally, the preparation of new compounds through the condensation of tropolone with other functional groups is discussed. A review of contemporary studies conducted on tumor cell cultures, various types of bacteria, and laboratory animals reveals that tropolone series compounds exhibit a broad spectrum of biological effects. This renders them promising lead molecules for the development of various drugs. The primary mechanism of tropolones involves the coordination of cations at the active centers of metalloenzymes. The authors of the extant works propose various pathways and targets of their action.

Conclusion

Conclusion. Tropolones exhibit a broad spectrum of biological activity, encompassing antiviral, antimicrobial, and antitumor properties. The study of the structure-activity relationship, coupled with the accumulation of information on the chemical and physical properties of the obtained substances, has led to the development of more effective methods of synthesis and the production of tropolone series compounds with improved efficiency and selectivity. This efficacy has been confirmed in both in vitro and in vivo studies. However, the precise mechanism(s) through which tropolones exert their biological effects remain to be elucidated. Consequently, further research in this area is imperative to elucidate the precise mechanisms of tropolones.

трополоныхимическая структура трополоновсинтез трополоновбиологическая активностьопухолевая культура клетокмодели in vivotropoloneschemical structure of tropolonessynthesis of tropolonesbiological activity of tropolonestumor cell culturein vivo modelsReferencesPinjari R.R., Siddiqui A., Ahmed N.A. Concepts of alkaloids from natural sources. Newcastle upon Tyne: Cambridge Scholars Publishing, 2024: 146.Pinjari R.R., Siddiqui A., Ahmed N.A. Concepts of alkaloids from natural sources. Newcastle upon Tyne: Cambridge Scholars Publishing, 2024: 146.Dewar M.J.S. Structure of stipitatic acid. Nature. 1945; 155(3924): 50–51. doi: 10.1038/155050b0.Dewar M.J.S. Structure of stipitatic acid. Nature. 1945; 155(3924): 50–51. doi: 10.1038/155050b0.Ahluwalia V.K., Aggarwal R. Tropones and tropolones. 2023. 195–98. (Alicyclic Chemistry. 2th ed. Cham: Springer). doi: 10.1007/9783-031-36068-8_13.Ahluwalia V.K., Aggarwal R. Tropones and tropolones. 2023. 195–98. (Alicyclic Chemistry. 2th ed. Cham: Springer). doi: 10.1007/9783-031-36068-8_13.Pal D., Lal P. Tropolones and Thailandepsin B as lead-like natural compounds in the development of potent and selective histone deacetylase inhibitors. Current Drug Targets. 2023; 24(9): 698–717. doi: 10.2174/1389450124666230707144251.Pal D., Lal P. Tropolones and Thailandepsin B as lead-like natural compounds in the development of potent and selective histone deacetylase inhibitors. Current Drug Targets. 2023; 24(9): 698–717. doi: 10.2174/1389450124666230707144251.Кит О.И., Жукова Г.В., Толкачев О.Н., Сидельников Н.И., Фадеев Н.Б., Лукбанова Е.А., Шихлярова А.И. Противоопухолевые факторы природного происхождения и некоторые подходы к разработке эффективных схем фитотерапии в онкологии (обзор литературы с включением результатов собственных исследований). Вопросы онкологии. 2022; 68(5): 527–38. doi: 10.37469/0507-3758-2022-68-5-527-538. EDN: BTTJTN.Kit O.I., Zhukova G.V., Tolkachev O.N., Sidelnikov N.I., Fadeev N.B., Lukbanova E.A., Shikhlyarova A.I. Antitumor factors of natural origin and some approaches to the development of effective regimens of phytotherapy in oncology (literature review including the findings of authors’ own research). Problems in Oncology. 2022; 68(5): 527–38. (in Russian). doi: 10.37469/0507-3758-2022-68-5-527-538. EDN: BTTJTN.Nozoe T. Über die farbstoffe im holzteile des “hinokl”-baumes. i. hinokitin und hinokitiol (Vorläufige Mitteilung). Bulletin of the Chemical Society of Japan. 1936; 11(3): 295–98. doi: 10.1246/bcsj.11.295.Nozoe T. Über die farbstoffe im holzteile des “hinokl”-baumes. i. hinokitin und hinokitiol (Vorläufige Mitteilung). Bulletin of the Chemical Society of Japan. 1936; 11(3): 295–98. doi: 10.1246/bcsj.11.295.Hongjie L.I.A.N.G., Siyu L.I. Research overview of secondary metabolite hinokitiol from plant. Chinese Journal of Pesticide Science. 2023; 25(4): 779–87. doi: 10.16801/j.issn.1008-7303.2023.0045.Hongjie L.I.A.N.G., Siyu L.I. Research overview of secondary metabolite hinokitiol from plant. Chinese Journal of Pesticide Science. 2023; 25(4): 779–87. doi: 10.16801/j.issn.1008-7303.2023.0045.Sardana K., Sinha S., Sachdeva S. Colchicine in dermatology: Rediscovering an old drug with novel uses. Indian Dermatol Online J. 2020; 11(5): 693–700. doi: 10.4103/idoj.IDOJ_475_20.Sardana K., Sinha S., Sachdeva S. Colchicine in dermatology: Rediscovering an old drug with novel uses. Indian Dermatol Online J. 2020; 11(5): 693–700. doi: 10.4103/idoj.IDOJ_475_20.Mitev V. Colchicine-the divine medicine against COVID-19. J Pers Med. 2024; 14(7): 756. doi: 10.3390/jpm14070756.Mitev V. Colchicine-the divine medicine against COVID-19. J Pers Med. 2024; 14(7): 756. doi: 10.3390/jpm14070756.Халецкий А.М. Фармацевтическая химия. Л., Медицина. 1966. 763 с.Khaletskiy A.M. Pharmaceutical chemistry. Leningrad., 1966: 763 p. (in Russian).Schiavone D.V., Kapkayeva D.M., Li Q., Woodson M.E., Gazquez Casals A., Morrison L.A. Tavis J.E., Murelli R.P. Synthesis of polyoxygenated tropolones and their antiviral activity against hepatitis B virus and herpes simplex virus‐1. Chemistry. 2022; 28(10): e202104112. doi: 10.1002/chem.202104112.Schiavone D.V., Kapkayeva D.M., Li Q., Woodson M.E., Gazquez Casals A., Morrison L.A. Tavis J.E., Murelli R.P. Synthesis of polyoxygenated tropolones and their antiviral activity against hepatitis B virus and herpes simplex virus‐1. Chemistry. 2022; 28(10): e202104112. doi: 10.1002/chem.202104112.Liu N., Song W., Schienebeck C.M., Zhang M., Tang W. Synthesis of naturally occurring tropones and tropolones. Tetrahedron. 2014; 70(49): 9281–305. doi: 10.1016/j.tet.2014.07.065.Liu N., Song W., Schienebeck C.M., Zhang M., Tang W. Synthesis of naturally occurring tropones and tropolones. Tetrahedron. 2014; 70(49): 9281–305. doi: 10.1016/j.tet.2014.07.065.Guo H., Roman D., Beemelmanns C. Tropolone natural products. Natural Product Reports. 2019; 36(8): 1137–55. doi: 10.1039/c8np00078f.Guo H., Roman D., Beemelmanns C. Tropolone natural products. Natural Product Reports. 2019; 36(8): 1137–55. doi: 10.1039/c8np00078f.Cook J.W., Dickson G.T., Jack J., Loudon J.D., McKeown J., MacMillan J., Williamson W.F. 30. Colchicine and related compounds. Part IX. Journal of the Chemical Society (Resumed). 1950; 139–47. doi: 10.1039/jr9500000139.Cook J.W., Dickson G.T., Jack J., Loudon J.D., McKeown J., MacMillan J., Williamson W.F. 30. Colchicine and related compounds. Part IX. Journal of the Chemical Society (Resumed). 1950; 139–47. doi: 10.1039/jr9500000139.Doering W.V.E., Knox L.H. Synthesis of tropolone. Journal of the American Chemical Society. 1950; 72(5): 2305–306. doi: 10.1021/ja01161a533.Doering W.V.E., Knox L.H. Synthesis of tropolone. Journal of the American Chemical Society. 1950; 72(5): 2305–306. doi: 10.1021/ja01161a533.Coşkun A., Güney M., Daştan A., Balci M. Oxidation of some alkoxy-cycloheptatriene derivatives: unusual formation of furan and furanoids from cycloheptatrienes. Tetrahedron. 2007; 63(23): 4944–50. doi: 10.1016/j.tet.2007.03.145.Coşkun A., Güney M., Daştan A., Balci M. Oxidation of some alkoxy-cycloheptatriene derivatives: unusual formation of furan and furanoids from cycloheptatrienes. Tetrahedron. 2007; 63(23): 4944–50. doi: 10.1016/j.tet.2007.03.145.Meck C., Mohd N., Murelli R.P. An oxidopyrylium cyclization/ ring-opening route to polysubstituted α-hydroxytropolones. Organic Letters. 2012; 14(23): 5988–91. doi: 10.1021/ol302892g.Meck C., Mohd N., Murelli R.P. An oxidopyrylium cyclization/ring-opening route to polysubstituted α-hydroxytropolones. Organic Letters. 2012; 14(23): 5988–91. doi: 10.1021/ol302892g.Pradhan P., Das I., Debnath S., Parveen S., Das T. Synthesis of substituted tropones and advancement for the construction of structurally significant skeletons. Chemistry Select. 2022; 7(23): e202200440. doi: 10.1002/slct.202200440.Pradhan P., Das I., Debnath S., Parveen S., Das T. Synthesis of substituted tropones and advancement for the construction of structurally significant skeletons. Chemistry Select. 2022; 7(23): e202200440. doi: 10.1002/slct.202200440.Gusakov E.A., Sayapin Y.A., Vetrova E.V., Lukbanova E.A., Alilueva E.V., Kolodina A.A., Tkachev V.V., Tupaeva I.O., Lisovin A.V., Steglenko D.V., Krasnikova T.A., Nikogosov M.V., Goncharova A.S., Metelitsa A.V., Aldoshin S.M., Minkin V.I. Synthesis, molecular structure and biological activity of novel bis-1, 3-tropolones based on 4-chloro-2, 7-dimethyl-1, 8-naphthyridine. Mendeleev Communications. 2024; 34(3): 357–61. doi: 10.1016/j.mencom.2024.04.015.Gusakov E.A., Sayapin Y.A., Vetrova E.V., Lukbanova E.A., Alilueva E.V., Kolodina A.A., Tkachev V.V., Tupaeva I.O., Lisovin A.V., Steglenko D.V., Krasnikova T.A., Nikogosov M.V., Goncharova A.S., Metelitsa A.V., Aldoshin S.M., Minkin V.I. Synthesis, molecular structure and biological activity of novel bis-1, 3-tropolones based on 4-chloro-2, 7-dimethyl-1, 8-naphthyridine. Mendeleev Communications. 2024; 34(3): 357–61. doi: 10.1016/j.mencom.2024.04.015.Mark M. The international problem of HIV/AIDS in the modern world: a comprehensive review of political, economic, and social impacts. Res Output J Public Health Med. 2024; 42: 47–52. doi: 10.59298/ROJPHM/2024/414752.Mark M. The international problem of HIV/AIDS in the modern world: a comprehensive review of political, economic, and social impacts. Res Output J Public Health Med. 2024; 42: 47–52. doi: 10.59298/ROJPHM/2024/414752.Wei F., da Silva-Júnior E.F., Liu X., Zhan P. HIV-1 and HBV RNase H as metal-chelating inhibitors: discovery and medicinal chemistry strategies. 2021. P. 585–602. (Shamim I., Ahmad, Ed. Human Viruses: Diseases, Treatments and Vaccines; Wollaton, Nottingham. Springer. 2021. 745 p. doi: 10.1007/978-3-030-71165-8. ISBN: 978-3-030-71164-1.Wei F., da Silva-Júnior E.F., Liu X., Zhan P. HIV-1 and HBV RNase H as metal-chelating inhibitors: discovery and medicinal chemistry strategies. 2021. P. 585–602. (Shamim I., Ahmad, Ed. Human Viruses: Diseases, Treatments and Vaccines; Wollaton, Nottingham. Springer. 2021. 745 p. doi: 10.1007/978-3-030-71165-8. ISBN: 978-3-030-71164-1.World Health Organization. Hepatitis B. [Internet]. [cited 08.01.2025]. URL: https://www.who.int/news-room/fact-sheets/detail/ hepatitis-b.World Health Organization. Hepatitis B. [Internet]. [cited 08.01.2025]. URL: https://www.who.int/news-room/fact-sheets/detail/hepatitis-b.Woodson M.E., Mottaleb M.A., Murelli R.P., Tavis J.E. In vitro evaluation of tropolone absorption, metabolism, and clearance. Antiviral Res. 2023; 220: 105762. doi: 10.1016/j.antiviral.2023.105762.Woodson M.E., Mottaleb M.A., Murelli R.P., Tavis J.E. In vitro evaluation of tropolone absorption, metabolism, and clearance. Antiviral Res. 2023; 220: 105762. doi: 10.1016/j.antiviral.2023.105762.World Health Organization. Herpes simplex virus. [Internet]. [cited 08.01.2025]. URL: https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus.World Health Organization. Herpes simplex virus. [Internet]. [cited 08.01.2025]. URL: https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus.Cao K., Zhang Y., Yao Q., Peng Y., Pan Q., Jiao Q., Ren K., Sun F., Zhang Q., Guo R., Zhang J., Chen T. Hypericin blocks the function of HSV-1 alkaline nuclease and suppresses viral replication. J Ethnopharmacol. 2022; 296: 115524. doi: 10.1016/j.jep.2022.115524.Cao K., Zhang Y., Yao Q., Peng Y., Pan Q., Jiao Q., Ren K., Sun F., Zhang Q., Guo R., Zhang J., Chen T. Hypericin blocks the function of HSV-1 alkaline nuclease and suppresses viral replication. J Ethnopharmacol. 2022; 296: 115524. doi: 10.1016/j.jep.2022.115524.Wan J., Wang M., Cheng A., Zhang W., Yang Q., Tian B., Ou X., Sun D., He Y., Zhao X., Wu Y., Zhang S., Huang J., Wu Z., Yu Y., Zhang L., Zhu D., Liu M., Chen S., Jia R. Multiple functions of the herpesvirus UL14 gene product in viral infection. Front Microbiol. 2024; 15: 1483022. doi: 10.3389/fmicb.2024.1483022.Wan J., Wang M., Cheng A., Zhang W., Yang Q., Tian B., Ou X., Sun D., He Y., Zhao X., Wu Y., Zhang S., Huang J., Wu Z., Yu Y., Zhang L., Zhu D., Liu M., Chen S., Jia R. Multiple functions of the herpesvirus UL14 gene product in viral infection. Front Microbiol. 2024; 15: 1483022. doi: 10.3389/fmicb.2024.1483022.Cao F., Orth C., Donlin M.J., Adegboyega P., Meyers M.J., Murelli R.P., Elagawany M., Elgendy B., Tavis J.E. Synthesis and evaluation of troponoids as a new class of antibiotics. ACS Omega. 2018; 3(11): 15125–33. doi: 10.1021/acsomega.8b01754.Cao F., Orth C., Donlin M.J., Adegboyega P., Meyers M.J., Murelli R.P., Elagawany M., Elgendy B., Tavis J.E. Synthesis and evaluation of troponoids as a new class of antibiotics. ACS Omega. 2018; 3(11): 15125–33. doi: 10.1021/acsomega.8b01754.Nakano K., Chigira T., Miyafusa T., Nagatoishi S., Caaveiro J.M., Tsumoto K. Discovery and characterization of natural tropolones as inhibitors of the antibacterial target CapF from Staphylococcus aureus. Sci Rep. 2015; 5(1): 15337. doi: 10.1038/srep15337.Nakano K., Chigira T., Miyafusa T., Nagatoishi S., Caaveiro J.M., Tsumoto K. Discovery and characterization of natural tropolones as inhibitors of the antibacterial target CapF from Staphylococcus aureus. Sci Rep. 2015; 5(1): 15337. doi: 10.1038/srep15337.Le C.Y., Ye Y.J., Xu J., Li L., Feng X.Q., Chen N.P., Zhu B.Q., Ding Z.S., Qian C.D. Hinokitiol selectively enhances the antibacterial activity of tetracyclines against Staphylococcus aureus. MicrobiolSpectr. 2023; 11(2): e03205-22. doi: 10.1128/spectrum.03205-22.Le C.Y., Ye Y.J., Xu J., Li L., Feng X.Q., Chen N.P., Zhu B.Q., Ding Z.S., Qian C.D. Hinokitiol selectively enhances the antibacterial activity of tetracyclines against Staphylococcus aureus. MicrobiolSpectr. 2023; 11(2): e03205-22. doi: 10.1128/spectrum.03205-22.Siegel R.L., Miller K.D., Wagle N.S., Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023; 73(1): 17–48. doi: 10.3322/caac.21763.Siegel R.L., Miller K.D., Wagle N.S., Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023; 73(1): 17–48. doi: 10.3322/caac.21763.Liu B., Zhou H., Tan L., Siu K.T.H., Guan X.Y. Exploring treatment options in cancer: tumor treatment strategies. Signal Transduct Target Ther. 2024; 9(1): 175. doi: 10.1038/s41392-024-01856-7.Liu B., Zhou H., Tan L., Siu K.T.H., Guan X.Y. Exploring treatment options in cancer: tumor treatment strategies. Signal Transduct Target Ther. 2024; 9(1): 175. doi: 10.1038/s41392-024-01856-7.Турсунова Н.В., Чурин Б.В., Клинникова М.Г. Противоопухолевая активность соединений природного происхождения. Современные проблемы науки и образования. 2018; (5): 201. doi: 10.17513/spno.28056. EDN: YMRMKL.Tursunova N.V., Churin B.V., Klinnikova M.G. Anti-tumor activity of some natural compounds. Modern Problems of Science and Education. 2018; (5): 201. (in Russian). doi: 10.17513/spno.28056. EDN: YMRMKL.Haney S.L., Feng D., Kollala S.S., Chhonker Y.S., Varney M.L., Williams J.T., Ford J.B., Murry D.J., Holstein S.A. Investigation of the activity of a novel tropolone in osteosarcoma. Drug Develop Res. 2024; 85(1): e22129. doi: 10.1002/ddr.22129.Haney S.L., Feng D., Kollala S.S., Chhonker Y.S., Varney M.L., Williams J.T., Ford J.B., Murry D.J., Holstein S.A. Investigation of the activity of a novel tropolone in osteosarcoma. Drug Develop Res. 2024; 85(1): e22129. doi: 10.1002/ddr.22129.Chiang Y.F., Huang K.C., Chen H.Y., Hamdy N.M., Huang T.C., Chang H.Y., Shieh T.M., Huang Y.J., Hsia S.M. Hinokitiol inhibits breast cancer cells in vitro stemness-progression and self-renewal with apoptosis and autophagy modulation via the CD44/Nanog/SOX2/Oct4 pathway. Int J Mol Sci. 2024; 25(7): 3904. doi: 10.3390/ijms25073904.Chiang Y.F., Huang K.C., Chen H.Y., Hamdy N.M., Huang T.C., Chang H.Y., Shieh T.M., Huang Y.J., Hsia S.M. Hinokitiol inhibits breast cancer cells in vitro stemness-progression and self-renewal with apoptosis and autophagy modulation via the CD44/Nanog/SOX2/Oct4 pathway. Int J Mol Sci. 2024; 25(7): 3904. doi: 10.3390/ijms25073904.Haas M., Lenz T., Kadletz-Wanke L., Heiduschka G., Jank B.J. The radiosensitizing effect of β-Thujaplicin, a tropolone derivative inducing S-phase cell cycle arrest, in head and neck squamous cell carcinomaderived cell lines. Invest New Drugs. 2022; 40(4): 700–708. doi: 10.1007/s10637-022-01229-3.Haas M., Lenz T., Kadletz-Wanke L., Heiduschka G., Jank B.J. The radiosensitizing effect of β-Thujaplicin, a tropolone derivative inducing S-phase cell cycle arrest, in head and neck squamous cell carcinomaderived cell lines. Invest New Drugs. 2022; 40(4): 700–708. doi: 10.1007/s10637-022-01229-3.Ibragimov A.A., Enikeeva Z.M., Agzamova N.A., Salihov F.S., Rahimov O.A., Askarova M.T. Investigation of mechanism activity of antitumor and radiosensitizing activity of preparations К-26 and K-26w. Am J Biomed Life Sci. 2020; 8(5): 131–36. doi: 10.11648/j.ajbls.20200805.12.Ibragimov A.A., Enikeeva Z.M., Agzamova N.A., Salihov F.S., Rahimov O.A., Askarova M.T. Investigation of mechanism activity of antitumor and radiosensitizing activity of preparations К-26 and K-26w. Am J Biomed Life Sci. 2020; 8(5): 131–36. doi: 10.11648/j.ajbls.20200805.12.Комарова Е.Ф., Лукбанова Е.А., Дженкова Е.А., Гончарова А.С., Заикина Е.В., Гурова С.В., Галина А.В., Курбанова Л.К., Миндарь М.В., Ходакова Д.В., Гусарева М.С. Зинькович М.С. Иммуногистохимическая оценка возможных механизмов противоопухолевого действия 2-(6, 8-диметил-5-нитро-4-хлорхинолин-2-ил)-5, 6, 7-трихлор-1, 3-трополона на PDX-моделях рака легкого. Южно-российский онкологический журнал. 2023; 4(1): 6–13. doi: 10.37748/26869039-2023-4-1-1. EDN: ATEHFO.Komarova E.F., Lukbanova E.A., Dzhenkova E.A., Goncharova A.S., Zaikina E.V., Gurova S.V., Galina A.V., Kurbanova L.K., Mindar M.V., Khodakova D.V., Gusareva M.S., Zinkovich M.S. Immunohistochemical assessment of possible anticancer effect mechanisms of 2-(6,8-dimethyl-5-nitro-4-chloroquinoline-2-yl)-5,6,7trichloro-1,3-tropolone in PDX models of lung cancer. South Russian Journal of Cancer. 2023; 4(1): 6–13. (in Russian). doi: 10.37748/26869039-2023-4-1-1. EDN: ATEHFO.Ni Y.J., Huang Z.N., Li H.Y., Lee C.C., Tyan Y.C., Yang M.H., Pangilinan C.R., Wu L.H., Chiang Y.C., Lee C.H. Hinokitiol impedes tumor drug resistance by suppressing protein kinase B/mammalian targets of rapamycin axis. J Cancer. 2022; 13(6): 1725–33. doi: 10.7150/jca.69449.Ni Y.J., Huang Z.N., Li H.Y., Lee C.C., Tyan Y.C., Yang M.H., Pangilinan C.R., Wu L.H., Chiang Y.C., Lee C.H. Hinokitiol impedes tumor drug resistance by suppressing protein kinase B/mammalian targets of rapamycin axis. J Cancer. 2022; 13(6): 1725–33. doi: 10.7150/jca.69449.Wang D.D., Zhang R., Tang L.Y., Ao M.R., Jia J.M., Wang A.H. Identification of diterpenoids from Salvia castanea Diels f. tomentosa Stib and their antitumor activities. Bioorg Chem. 2024; 151: 107701. doi: 10.1016/j.bioorg.2024.107701.Wang D.D., Zhang R., Tang L.Y., Ao M.R., Jia J.M., Wang A.H. Identification of diterpenoids from Salvia castanea Diels f. tomentosa Stib and their antitumor activities. Bioorg Chem. 2024; 151: 107701. doi: 10.1016/j.bioorg.2024.107701.

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