Selected Plant Triterpenoids and Their Derivatives as Antiviral Agents

. 2023 Nov 22 ; 28 (23) : . [epub] 20231122

Jazyk angličtina Země Švýcarsko Médium electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid38067449

Grantová podpora
FV30300 Ministry of Industry and Commerce, Czech Republic (MPO)

The results of the most recent investigation of triterpenoid-based antiviral agents namely in the HIV-1 and HSV-1 treatment were reviewed and summarized. Several key historical achievements are included to stress consequences and continuity in this research. Most of the agents studied belong to a series of compounds derived from betulin or betulinic acid, and their synthetic derivative is called bevirimat. A termination of clinical trials of bevirimat in Phase IIb initiated a search for more successful compounds partly derived from bevirimat or designed independently of bevirimat structure. Surprisingly, a majority of bevirimat mimics are derivatives of betulinic acid, while other plant triterpenoids, such as ursolic acid, oleanolic acid, glycyrrhetinic acid, or other miscellaneous triterpenoids, are relatively rarely involved in a search for a novel antiviral agent. Therefore, this review article is divided into three parts based on the leading triterpenoid core structure.

Zobrazit více v PubMed

Liu Y., Yang L., Wang H., Xiong Y. Recent advances in antiviral activities of triterpenoids. Pharmaceuticals. 2022;15:1169. doi: 10.3390/ph15101169. PubMed DOI PMC

Sander W.J., O’Neill H.G., Pohl C.H. Prostaglandin E(2) as a modulator of viral infections. Front. Physiol. 2017;8:89. doi: 10.3389/fphys.2017.00089. PubMed DOI PMC

He W., Gao Y., Wen Y., Ke X., Ou Z., Li Y., He H., Chen Q. Detection of virus-related sequences associated with potential etiologies of hepatitis in liver tissue samples from rats, mice, shrews, and bats. Front. Microbiol. 2021;12:653873. doi: 10.3389/fmicb.2021.653873. PubMed DOI PMC

Yang X.W. Antiviral effect of glycyrrhizic acid. Mod. Chin. Med. 2020;22:533–541.

Yang J., Yue L., Yang Z., Miao Y., Ouyang R., Hu Y. Metal-based nanomaterials: Work as drugs and carriers against viral infections. Nanomaterials. 2021;11:2129. doi: 10.3390/nano11082129. PubMed DOI PMC

Finsterer J. Neurological side effects of SARS-CoV-2 vaccinations. Acta Neurol. Scand. 2022;145:5–9. doi: 10.1111/ane.13550. PubMed DOI PMC

Hacisuleyman E., Hale C., Saito Y., Blachere N.E., Bergh M., Conlon E.G., Schaefer-Babajew D.J., DaSilva J., Muecksch F., Gaebler C., et al. Vaccine breakthrough infections with SARS-CoV-2 variants. N. Engl. J. Med. 2021;384:2212–2218. doi: 10.1056/NEJMoa2105000. PubMed DOI PMC

Yi Y., Li J., Lai X., Zhang M., Kuang Y., Bao Y.-O., Yu R., Hong W., Muturi E., Xue H., et al. Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection. J. Adv. Res. 2022;36:201–210. doi: 10.1016/j.jare.2021.11.012. PubMed DOI PMC

Pu J.Y., He L., Wu S.Y., Zhang P., Huang X. Anti-virus research of triterpenoids in licorice. Chin. J. Virol. 2013;29:673–679. PubMed

Pornillos O., Ganser-Pornillos B.K. Maturation of retroviruses. Curr. Opin. Virol. 2019;36:47–55. doi: 10.1016/j.coviro.2019.05.004. PubMed DOI PMC

Kanamoto T., Kashiwada Y., Kanbara K., Gotoh K., Yoshimori M., Goto T., Sano K., Nakashima H. Anti-human immunodeficiency virus activity of YK-FH312 (a betulinic acid derivative), a novel compound blocking viral maturation. Antimicrob. Agents Chemother. 2001;45:1225–1230. doi: 10.1128/AAC.45.4.1225-1230.2001. PubMed DOI PMC

Zhou J., Yuan X., Dismuke D., Forshey B.M., Lundquist C., Lee K.-H., Aiken C., Chen C.H. Small-molecule inhibition of human immunodeficiency virus type 1 replication by specific targeting of the final step of virion maturation. J. Virol. 2004;78:922–929. doi: 10.1128/JVI.78.2.922-929.2004. PubMed DOI PMC

Adamson C.S., Ablan S.D., Boeras I., Goila-Gaur R., Soheilian F., Nagashima K., Li F., Salzwedel K., Sakalian M., Wild C.T., et al. In vitro resistance to the human immunodeficiency virus type 1 maturation inhibitor PA-457 (Bevirimat) J. Virol. 2006;80:10957–10971. doi: 10.1128/JVI.01369-06. PubMed DOI PMC

Pak A.J., Purdy M.D., Yeager M., Voth G.A. Preservation of HIV-1 gag helical bundle symmetry by bevirimat is central to maturation inhibition. J. Am. Chem. Soc. 2021;143:19137–19148. doi: 10.1021/jacs.1c08922. PubMed DOI PMC

Purdy M.D., Shi D., Christowicz J., Hattne J., Goner T., Yeager M. MicroED structures of HIV-1GagCTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat. Proc. Natl. Acad. Sci. USA. 2018;115:13258–13263. doi: 10.1073/pnas.1806806115. PubMed DOI PMC

Adamson C.S., Salzwedel K., Freed E.O. Virus maturation as a new HIV-1 therapeutic target. Expert Opin. Ther. Targets. 2009;13:895–908. doi: 10.1517/14728220903039714. PubMed DOI PMC

Hashimoto F., Kashiwada Y., Cosentino L.M., Chen C.-H., Garrett P.E., Lee K.-H. Anti-AIDS agents-XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives. Bioorg. Med. Chem. 1997;5:2133–2143. doi: 10.1016/S0968-0896(97)00158-2. PubMed DOI

Lee K.-H. Discovery and development of natural product-derived chemotherapeutic agents based on a medicinal chemistry approach. J. Nat. Prod. 2010;73:500–516. doi: 10.1021/np900821e. PubMed DOI PMC

Van Baelen K., Salzwedel K., Rondelez E., Van Eygen V., De Vos S., Verheyen A., Steegen K., Verlinden Y., Allaway G.P., Stuyver L.J. Susceptibility of human immunodeficiency virus type 1 to the maturation inhibitor bevirimat is modulated by baseline polymorphisms in gag spacer peptide 1. Antimicrob. Agents Chemother. 2009;53:2185–2188. doi: 10.1128/AAC.01650-08. PubMed DOI PMC

Adamson C.S., Sakalian M., Salzwedel K., Freed E.O. Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV-1 maturation inhibitor bevirimat. Retrovirology. 2010;7:36. doi: 10.1186/1742-4690-7-36. PubMed DOI PMC

Liu X., Main D., Ma Y., He B. Herpes simplex virus 1 inhibits TANK-binding kinase 1 through formation of the Us11-Hsp90 complex. J. Virol. 2018;92:e00402-18. doi: 10.1128/JVI.00402-18. PubMed DOI PMC

Whitley R.J. Herpes simplex encephalitis: Adolescents and adults. Antivir. Res. 2006;71:141–148. doi: 10.1016/j.antiviral.2006.04.002. PubMed DOI

Navid M.H., Laszczyk-Lauer M.N., Reichling J., Schnitzler P. Pentacyclic triterpenes in birch bark extract inhibit early step of herpes simplex virus type 1 replication. Phytomedicine. 2014;21:1273–1280. doi: 10.1016/j.phymed.2014.06.007. PubMed DOI

Ye J., Wang Z., Jia J., Li F., Wang Y., Jiang Y., Wang Y., Ren Z., Pu H. Lupeol impairs herpes simplex virus type 1 replication by inhibiting the promoter activity of the viral immediate early gene α0. Acta Virol. 2021;65:254–263. doi: 10.4149/av_2021_302. PubMed DOI

Ramu R., Shirahatti P.S., Swamy S.N., Zameer F., Dhananjaya B.L., Prasad M.N.N. Assessment of in vivo antidiabetic properties of umbelliferone and lupeol constituents of banana (Musa sp. var. Nanjangud Rasa Bale) flower in hyperglycaemic rodent model. PLoS ONE. 2016;11:e0151135. PubMed PMC

Kolokotronis A., Doumas S. Herpes simplex virus infection, with particular reference to the progression and complications of primary herpetic gingivostomatitis. Clin. Microbiol. Infect. 2006;12:202–211. doi: 10.1111/j.1469-0691.2005.01336.x. PubMed DOI

Coen D.M., Schaffer P.A. Anti-herpesvirus drugs: A promising spectrum of new drugs and drug targets. Nat. Rev. Drug. Discov. 2003;2:278–288. doi: 10.1038/nrd1065. PubMed DOI

Pecak P., Orzechowska B., Chrobak E., Boryczka S. Novel betulin dicarboxylic acid ester derivatives as potent antiviral agents: Design, synthesis, biological evaluation, structure-activity relationship and in silico study. Eur. J. Med. Chem. 2021;225:113738. doi: 10.1016/j.ejmech.2021.113738. PubMed DOI

Amiri S., Dastghaib S., Ahmadi M., Mehrbod P., Khadem F., Behrouj H., Aghanoori M.R., Machaj F., Ghamsari M., Rosik J., et al. Betulin and its derivatives as novel compounds with different pharmacological effects. Biotechnol. Adv. 2020;38:107409. doi: 10.1016/j.biotechadv.2019.06.008. PubMed DOI

Kazakova O.B., Medvedeva N.I., Baikova I.P., Tolstikov G.A., Lopatina T.V., Yunusov M.S., Zaprutko L. Synthesis of triterpenoid acylates: Effective reproduction inhibitors of influenza A (H1N1) and papilloma viruses. Russ. J. Bioorg. Chem. 2010;36:771–778. doi: 10.1134/S1068162010060142. PubMed DOI PMC

Pavlova P.I., Savinova O.V., Nikolaeva S.N., Boreko E.I., Flekhter O.B. Antiviral activity of betulin, betulinic and betulonic acids against some enveloped and non-enveloped viruses. Fitoterapia. 2003;74:489–492. doi: 10.1016/S0367-326X(03)00123-0. PubMed DOI

Sun I.C., Shen J.K., Wang H.K., Cosentino L.M., Lee K.H. Anti-AIDS agents. 32. Synthesis and anti-HIV activity of betulin derivatives. Bioorg. Med. Chem. Lett. 1998;8:1267–1272. doi: 10.1016/S0960-894X(98)00202-9. PubMed DOI

Šarek J., Kvasnica M., Vlk M., Urban M., Džubák P., Hajdúch M. The potential of triterpenoids in the treatment of melanoma. In: Murph M., editor. Research on Melanoma—A Glimpse into Current Directions and Future Trends. InTech; Rijeka, Croatia: 2011. pp. 125–158. Chapter 7.

Kim D.S.H.L., Chen Z., Nguyen V.T., Pezzuto J.M., Qiu S., Lu Z.-Z. A concise semi-synthetic approach to betulinic acid from betulin. Synth. Commun. 1997;27:1607–1612. doi: 10.1080/00397919708006099. DOI

Alakurtti S., Mäkelä T., Koskimies S., Yli-Kauhaluoma J. Pharmacological properties of the ubiquitous natural product betulin. J. Eur. Pharm. Sci. 2006;29:1–13. doi: 10.1016/j.ejps.2006.04.006. PubMed DOI

Bildziukevich U., Özdemir Z., Wimmer Z. Recent achievements in medicinal and supramolecular chemistry of betulinic acid and its derivatives. Molecules. 2019;24:3546. doi: 10.3390/molecules24193546. PubMed DOI PMC

Özdemir Z., Wimmer Z. Selected plant triterpenoids and their amide derivatives in cancer treatment: A review. Phytochemistry. 2022;203:113340. doi: 10.1016/j.phytochem.2022.113340. PubMed DOI

Martin D.E., Salzwedel K., Allaway G.P. Bevirimat: A novel maturation inhibitor for the treatment of HIV-1 infection. Antivir. Chem. Chemother. 2008;19:107–113. doi: 10.1177/095632020801900301. PubMed DOI

Martin D.E., Blum R., Doto J., Galbraith H., Ballow C. Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers. Clin. Pharmacokinet. 2007;46:589–598. doi: 10.2165/00003088-200746070-00004. PubMed DOI

Tang J., Jones S.A., Jeffrey J.L., Mirianda S.R., Galardi C.M., Irlbeck D.M., Brown K.W., McDanal C.B., Johns B.A. Discovery of a novel and potent class of anti-HIV-1 maturation inhibitors with improved virology profile against gag polymorphisms. Bioorg. Med. Chem. Lett. 2017;27:2689–2694. doi: 10.1016/j.bmcl.2017.04.042. PubMed DOI

Marciniec K., Chrobak E., Dabrowska A., Bebenek E., Kadela-Tomanek M., Pecak P., Boryczka S. Phosphate derivatives of 3-carboxyacylbetulin: Synthesis, in vitro anti-HIV and molecular docking study. Biomolecules. 2020;10:1148. doi: 10.3390/biom10081148. PubMed DOI PMC

Sarkar S., Zadrozny K.K., Zadoroyhnyi R., Russell R.W., Quinn C.M., Kleinpeter A., Ablan S., Meshkin H., Perilla J.R., Freed E.O., et al. Structural basis of HIV-1 maturation inhibitor binding and activity. Nat. Commun. 2023;14:1237. doi: 10.1038/s41467-023-36569-y. PubMed DOI PMC

Coric P., Turcaud S., Souquet F., Briant L., Gay B., Royer J., Chazal N., Bouaziz S. Synthesis and biological evaluation of a new derivative of bevirimat that targets the Gag CA-SP1 cleavage site. Eur. J. Med. Chem. 2013;62:453–465. doi: 10.1016/j.ejmech.2013.01.013. PubMed DOI

Martin D.E., Blum R., Wilton J., Doto J., Galbraith H., Burgess G.L., Smith P.C., Ballow C. Safety and pharmacokinetics of bevirimat (PA-457), a novel inhibitor of human immunodeficiency virus maturation, in healthy volunteers. Antimicrob. Agents Chemother. 2007;51:3063–3066. doi: 10.1128/AAC.01391-06. PubMed DOI PMC

Smith P.F., Ogundele A., Forrest A., Wilton J., Salzwedel K., Doto J., Allaway G.P., Martin D.E. Phase I and II study of the safety, virological effect, and pharmacokinetics/pharmacodynamics of single-dose 3-O-(3’,3’-dimethylsuccinyl)betulinic acid (bevirimat) against human immunodeficiency virus infection. Antimicrob. Agents Chemother. 2007;51:3574–3581. doi: 10.1128/AAC.00152-07. PubMed DOI PMC

Regueiro-Ren A., Sit S.-Y., Chen Y., Chen J., Swidorski J.J., Liu Z., Venables B.L., Sin N.; Hartz, R.A.; Protack, T.; et al. The discovery of GSK3640254, a next-generation inhibitor of HIV-1 maturation. J. Med. Chem. 2022;65:11927–11948. doi: 10.1021/acs.jmedchem.2c00879. PubMed DOI

Hartz R.A., Xu L., Sit S.-Y., Chen J., Venables B.L., Lin Z., Zhang S., Li Z., Parker D., Simmons T.S., et al. Synthesis, structure−activity relationships, and in vivo evaluation of novel C-17 amine derivatives based on GSK3640254 as HIV-1 maturation inhibitors with broad spectrum activity. J. Med. Chem. 2022;65:15935–15966. doi: 10.1021/acs.jmedchem.2c01618. PubMed DOI

Meanwell N.A. Sub-stoichiometric modulation of viral targets-potent antiviral agents that exploit target vulnerability. ACS Med. Chem. Lett. 2023;14:1021–1030. doi: 10.1021/acsmedchemlett.3c00279. PubMed DOI PMC

Yuvraj H.C., Pal S., Nitz T.J., Wild C., Gaur R. Construction of a HIV-1 subtype C 3D model using homology modeling and in silico docking, molecular dynamics simulation, and MM-GBSA calculation of second-generation HIV-1 maturation inhibitor(s) J. Biomol. Struct. Dyn. 2023 doi: 10.1080/07391102.2023.2238079. epub ahead of print . PubMed DOI

Chrobak E., Marciniec K., Dabrowska A., Pecak P., Bebenek E., Kadela-Tomanek M., Bak A., Jastrzebska M., Boryczka S. New phosphorus analogs of bevirimat: Synthesis, evaluation of anti-HIV-1 activity and molecular docking study. Int. J. Mol. Sci. 2019;20:5209. doi: 10.3390/ijms20205209. PubMed DOI PMC

Zhao L., He H.H., Ou-Yang T., Liu D.F., Jiang C.H., Yang H.P., Wang P., Xie N., Yan S.S. Pre-clinical pharmacological profile of QF-036, a potent HIV-1 maturation inhibitor. Basic Clin. Pharm. Toxicol. 2021;128:275–285. doi: 10.1111/bcpt.13504. PubMed DOI

Zhao Y., Chen C.-H., Morris-Natschke S.L., Lee K.-H. Design, synthesis, and structure activity relationship analysis of new betulinic acid derivatives as potent HIV inhibitors. Eur. J. Med. Chem. 2021;215:113287. doi: 10.1016/j.ejmech.2021.113287. PubMed DOI PMC

Wang C., Lu L., Na H., Li X., Wang Q., Jiang X., Xu X., Yu F., Zhang T., Li J., et al. Conjugation of a nonspecific antiviral sapogenin with a specific HIV fusion inhibitor: A promising strategy for discovering new antiviral therapeutics. J. Med. Chem. 2014;57:7342–7354. doi: 10.1021/jm500763m. PubMed DOI

Liu F., Wang Y.-N., Li Y., Ma S.-G., Qu J., Liu Y.-B., Niu C.-S., Tang Z.-H., Li Y.-H., Li L., et al. Minor nortriterpenoids from the twigs and leaves of Rhododendron latoucheae. J. Nat. Prod. 2018;81:1721–1733. doi: 10.1021/acs.jnatprod.7b01074. PubMed DOI

Khusnutdinova E., Galimova Z., Lobov A., Baikova I., Kazakova O., Thu H.N.T., Tuyen N.V., Gatilov Y., Csuk R., Serbian I., et al. Synthesis of messagenin and platanic acid chalcone derivatives and their biological potential. Nat. Prod. Res. 2022;36:5189–5198. doi: 10.1080/14786419.2021.1922904. PubMed DOI

Wang H.-Q., Ma S.-G., Zhang D., Li Y.-H., Qu J., Li Y., Liu Y.-B., Yu S.-S. Oxygenated pentacyclic triterpenoids from the stems and branches of Enkianthus chinensis. Bioorg. Chem. 2021;111:104866. doi: 10.1016/j.bioorg.2021.104866. PubMed DOI

Ogawa K., Nakamura S., Oguri H., Ryu K., Yoneda T., Hosoki R. Effective search of triterpenes with anti-HSV-1 activity using a classification model by logistic regression. Front. Chem. 2021;9:763794. doi: 10.3389/fchem.2021.763794. PubMed DOI PMC

Zhao X.-T., Yu M.-H., Su S.-Y., Shi X.-L., Lei C., Hou A.-J. Cycloartane triterpenoids from Pseudolarix amabilis and their antiviral activity. Phytochemistry. 2020;171:112229. doi: 10.1016/j.phytochem.2019.112229. PubMed DOI

Nejnovějších 20 citací...

Zobrazit více v
Medvik | PubMed

Cytotoxicity and Nanoassembly Characteristics of Aromatic Amides of Oleanolic Acid and Ursolic Acid

. 2025 May 27 ; 10 (20) : 20938-20948. [epub] 20250512

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...