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Synthesis of indole-based ferulic acid derivatives and in vitro evaluation of antiviral activity against SARS-CoV-2

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Abstract

The search for an effective small molecule against the severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) is a challenge that remains even after the end of the Coronavirus disease 2019 (COVID-19) global health emergency. The indole-based ferulic acid derivatives were synthesized in this work and evaluated for their in vitro cytotoxic profiles and anti-SARS-CoV-2 activity. Compounds 1 and 2 decreased the number of genomic copies of SARS-CoV-2 in a dose-dependent manner, with IC50 values of 70.85 µM and 68.28 µM, respectively, with no significant cytotoxicity up to 100 µM against uninfected Vero cells. In order to search for a possible molecular target of these compounds, their activity against the two SARS-CoV-2 cysteine proteases, Mpro and PLpro, in addition to the human cysteine protease cathepsin L (hCatL) was investigated. However, they did not display significant activity against any of these proteases and, therefore, their mechanism of action remains unclear. Our findings suggest that the activity may be related to antioxidant properties of 1 and 2, since the presence of a phenolic group is critical for the antiviral activity.

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References

  1. Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19:141–54. https://doi.org/10.1038/s41579-020-00459-7

    Article  CAS  PubMed  Google Scholar 

  2. Wu JT, Leung K, Leung GM. Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study. Lancet. 2020;395:689–97. https://doi.org/10.1016/S0140-6736(20)30260-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Adil MT, Rahman R, Whitelaw D, Jain V, Al-Taan O, Rashid F. et al. SARS-CoV-2 and the pandemic of COVID-19. Postgrad Med J. 2021;97:110–6. https://doi.org/10.1136/postgradmedj-2020-138386.

    Article  CAS  PubMed  Google Scholar 

  4. Huang Y, Yang C, Xu X, Xu W, Liu S. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41:1141–9. https://doi.org/10.1038/s41401-020-0485-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L. et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science. 2020;368:409–12. https://doi.org/10.1126/science.abb3405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rut W, Lv Z, Zmudzinski M, Patchett S, Nayak D, Snipas SJ. et al. Activity profiling and crystal structures of inhibitor-bound SARS-CoV-2 papain-like protease: A framework for anti-COVID-19 drug design. Sci Adv. 2020;6:eabd4596. https://doi.org/10.1126/sciadv.abd4596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hillen HS, Kokic G, Farnung L, Dienemann C, Tegunov D, Cramer P. Structure of replicating SARS-CoV-2 polymerase. Nature 2020;584:154–6. https://doi.org/10.1038/s41586-020-2368-8

    Article  CAS  PubMed  Google Scholar 

  8. Ashhurst AS, Tang AH, Fajtová P, Yoon MC, Aggarwal A, Bedding MJ. et al. Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L. J Med Chem. 2022;65:2956–70. https://doi.org/10.1021/acs.jmedchem.1c01494.

    Article  CAS  PubMed  Google Scholar 

  9. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S. et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181:271–.E8. https://doi.org/10.1016/j.cell.2020.02.052.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Liu T, Luo S, Libby P, Shi GP. Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients. Pharmacol Ther. 2020;213:107587. https://doi.org/10.1016/j.pharmthera.2020.107587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yan R, Zhang Y, Li Y, **a L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367:1444–8. https://doi.org/10.1126/science.abb2762

    Article  PubMed  PubMed Central  Google Scholar 

  12. Huang J, Song W, Huang H, Sun Q. Pharmacological Therapeutics Targeting RNA-Dependent RNA Polymerase, Proteinase and Spike Protein: From Mechanistic Studies to Clinical Trials for COVID-19. J Clin Med. 2020;9:1131. https://doi.org/10.3390/jcm9041131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Shang J, Wan Y, Luo C, Ye G, Geng Q, Auerbach A. et al. Cell Entry Mechanisms of SARS-CoV-2. Proc Natl Acad USA. 2020;117:11727–34. https://doi.org/10.1073/pnas.2003138117.

    Article  CAS  Google Scholar 

  14. Narayanan A, Narwal M, Majowicz SA, Varricchio C, Toner SA, Ballatore C, et al. Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay. Comm Biol. 2022;5. https://doi.org/10.1038/s42003-022-03090-9.

  15. Yang H, Rao Z. Structural biology of SARS-CoV-2 and implications for therapeutic development. Nature Rev Microbiol. 2021;19:685–700. https://doi.org/10.1038/s41579-021-00630-8

    Article  CAS  Google Scholar 

  16. Bhowmik D, Nandi R, Jagadeesan R, Kumar N, Prakash A, Kumar D. Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches. Infect Genet Evol. 2020;84:104451 https://doi.org/10.1016/j.meegid.2020.104451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Antonopoulou I, Sapountzaki E, Rova U, Christakopoulos P. Ferulic Acid From Plant Biomass: A Phytochemical With Promising Antiviral Properties. Front Nutr. 2022;8:777576 https://doi.org/10.3389/fnut.2021.777576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sgarbossa A, Giacomazza D, di Carlo M. Ferulic Acid: A Hope for Alzheimer’s Disease Therapy from Plants. Nutrients. 2015;7:5764–82. https://doi.org/10.3390/nu7075246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Liu Y, Shi L, Qiu W, Shi Y. Ferulic acid exhibits anti-inflammatory effects by inducing autophagy and blocking NLRP3 inflammasome activation. Mol Cell Toxicol. 2022;18:509–19. https://doi.org/10.1007/s13273-021-00219-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yin ZN, Wu WJ, Sun CZ, Liu HF, Chen WB, Zhan QP. et al. Antioxidant and Anti-inflammatory Capacity of Ferulic Acid Released from Wheat Bran by Solid-state Fermentation of Aspergillus niger. Biomed Environ Sci. 2019;32:11–21. https://doi.org/10.3967/bes2019.002.

    Article  CAS  PubMed  Google Scholar 

  21. Pernin A, Bosc V, Maillard MN, Dubois-Brissonnet F. Ferulic Acid and Eugenol Have Different Abilities to Maintain Their Inhibitory Activity Against Listeria monocytogenes in Emulsified Systems. Front Microbiol. 2019;10:137 https://doi.org/10.3389/fmicb.2019.00137

    Article  PubMed  PubMed Central  Google Scholar 

  22. Gan X, Wang Z, Hu D. Synthesis of Novel Antiviral Ferulic Acid-Eugenol and Isoeugenol Hybrids Using Various Link Reactions. J Agric Food Chem. 2021;69:13724–33. https://doi.org/10.1021/acs.jafc.1c05521

    Article  CAS  PubMed  Google Scholar 

  23. Stompor-Gorący M, Machaczka M. Recent Advances in Biological Activity, New Formulations and Prodrugs of Ferulic Acid. J Mol Sci. 2021;22:12889 https://doi.org/10.3390/ijms222312889

    Article  CAS  Google Scholar 

  24. El Gizawy HA, Boshra SA, Mostafa A, Mahmoud SH, Ismail MI, Alsfouk AA. et al. Pimenta dioica (L.) Merr. Bioactive Constituents Exert Anti-SARS-CoV-2 and Anti-Inflammatory Activities: Molecular Docking and Dynamics, In Vitro, and In Vivo Studies. Molecules. 2021;26:5844 https://doi.org/10.3390/molecules26195844.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Pasquereau S, Galais M, Bellefroid M, Angona IP, Morot-Bizot S, Ismaili L. et al. Ferulic acid derivatives block coronaviruses HCoV-229E and SARS-CoV-2 replication in vitro. Sci Rep. 2022;12:20309. https://doi.org/10.1038/s41598-022-24682-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Cascioferro S, Petri GL, Parrino B, Hassouni BE, Carbone D, Arizza V. et al. 3-(6-Phenylimidazo [2,1-b][1,3,4]thiadiazol-2-yl)-1H-Indole Derivatives as New Anticancer Agents in the Treatment of Pancreatic Ductal Adenocarcinoma. Molecules. 2020;25:329. https://doi.org/10.3390/molecules25020329.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cascioferro S, Attanzio A, Di Sarno V, Musella S, Tesoriere L, Cirrincione G. et al. New 1,2,4-Oxadiazole Nortopsentin Derivatives with Cytotoxic Activity. Mar Drugs. 2019;17:35. https://doi.org/10.3390/md17010035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Carbone A, Parrino B, Cusimano M, Spanó V, Montalbano A, Barraja P. et al. New Thiazole Nortopsentin Analogues Inhibit Bacterial Biofilm Formation. Mar Drugs. 2018;16:274. https://doi.org/10.3390/md16080274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dhuguru J, Skouta R. Role of Indole Scaffolds as Pharmacophores in the Development of Anti-Lung Cancer Agents. Molecules. 2020;25:1615. https://doi.org/10.3390/molecules25071615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Almaraz-Girón MA, Calderón-Jaimes E, Carrillo AS, Díaz-Cervantes E, Alonso EC, Islas-Jácome A. et al. Search for Non-Protein Protease Inhibitors Constituted with an Indole and Acetylene Core. Molecules. 2021;26:3817. https://doi.org/10.3390/molecules26133817.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang X, Sacramento CQ, Jockusch S, Chaves OA, Tao C, Fintelman-Rodrigues N. et al. Combination of antiviral drugs inhibits SARS-CoV2 polymerase and exonuclease and demonstrates COVID-19 therapeutic potential in viral cell culture. Commun Biol. 2022;5:154 https://doi.org/10.1038/s42003-022-03101-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Zadeh NM, Asl NSM, Forouharnejad K, Ghadimi K, Parsa S, Mohammadi S, et al. Mechanism and adverse effects of COVID-19 drugs: a basic review. Int J Physiol Pathophysiol Pharmacol. 2021;13:102–9.

    CAS  Google Scholar 

  33. De Flora S, Balansky R, Maestra SL. Antioxidants and COVID-19. J Prev Med Hyg. 2021;62:1s3. https://doi.org/10.15167/2421-4248/jpmh2021.62.1S3.1895

    Article  Google Scholar 

  34. Rehman MF, Akhter S, Batool AI, Selamoglu Z, Sevindik M, Eman R. et al. Effectiveness of Natural Antioxidants against SARS-CoV-2? Insights from the In-Silico World. Antibiotics. 2021;10:1011 https://doi.org/10.3390/antibiotics10081011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Liu Y, Liang C, **n L, Ren X, Tian L, Ju X. et al. The development of Coronavirus 3C-Like protease (3CLpro) inhibitors from 2010 to 2020. Eur J Med Chem. 2020;206:112711 https://doi.org/10.1016/j.ejmech.2020.112711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Vankadara S, Wong YX, Liu B, See YY, Tan LH, Tan QW. et al. A Head-to-Head Comparison of the Inhibitory Activities of 15 Peptidomimetic SARS-CoV-2 3CLpro Inhibitors. Bioorg Med Chem Lett. 2021;48:128263 https://doi.org/10.1016/j.bmcl.2021.128263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dai W, Jochmans D, **e H, Yang H, Li J, Su H. et al. Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2. J Med Chem. 2022;65:2794–808. https://doi.org/10.1021/acs.jmedchem.0c02258.

    Article  CAS  PubMed  Google Scholar 

  38. Azevedo L, Serafim MSM, Maltarollo VG, Grabrucker AM, Granato D. Atherosclerosis Fate in the Era of Tailored Functional Foods: Evidence-based Guidelines Elicited from Structure-and Ligand-Based Approaches. Trends Food Sci Technol. 2022;128:75–89. https://doi.org/10.1016/j.tifs.2022.07.010

    Article  CAS  Google Scholar 

  39. Serafim MS, Lavorato SN, Kronenberger T, Sousa YV, Oliveira GP, dos Santos SG. et al. Antibacterial activity of synthetic 1,3-bis(aryloxy)propan-2-amines against Gram-positive bacteria. Microbiologyopen. 2019;8:e814 https://doi.org/10.1002/mbo3.814.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ashhurst AS, Tang AH, Fajtová P, Yoon MC, Aggarwal A, Bedding MJ. et al. Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L. J Med Chem. 2022;65:2956–70. https://doi.org/10.1021/acs.jmedchem.1c01494.

    Article  CAS  PubMed  Google Scholar 

  41. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S. et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181:271–80.E8. https://doi.org/10.1016/j.cell.2020.02.052.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Koenig SG, Dankwardt JW, Liu Y, Zhao H, Singh SP. A ligand-free, copper-catalyzed cascade sequence to indole-2-carboxylic esters. Tetrahedron Lett. 2010;51:6549–51. https://doi.org/10.1016/j.tetlet.2010.10.035

    Article  CAS  Google Scholar 

  43. Tsotinis A, Afroudakis PA, Davidson K, Prashar A, Sugden D. Design, synthesis, and melatoninergic activity of new azido- and isothiocyanato-substituted indoles. J Med Chem. 2007;50:6436–40. https://doi.org/10.1021/jm7010723

    Article  CAS  PubMed  Google Scholar 

  44. Boraei ATA, El Ashry ESH, Barakat A, Ghabbour HA. Synthesis of New Functionalized Indoles Based on Ethyl Indol-2-carboxylate. Molecules. 2016;21:333 https://doi.org/10.3390/molecules21030333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kaye M, Druce J, Tran T, Kostecki R, Chibo D, Morris J. et al. SARS-associated coronavirus replication in cell lines. Emerg Infect Dis. 2006;12:1 https://doi.org/10.3201/eid1201.050496.

    Article  Google Scholar 

  46. Lescure FX, Bouadma L, Nguyen D, Parisey M, Wicky PH, Behillil S. et al. Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis. 2020;20:697–706. https://doi.org/10.1016/S1473-3099(20)30200-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DKW, et al. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill. 2020;25 https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045.

  48. Mellott DM, Tseng CT, Drelich A, Fajtová P, Chenna BC, Kostomiris DH. et al. A Clinical-Stage Cysteine Protease Inhibitor blocks SARS-CoV-2 Infection of Human and Monkey Cells. ACS Chem Biol. 2021;16:642–50. https://doi.org/10.1021/acschembio.0c00875.

    Article  CAS  PubMed  Google Scholar 

  49. Pillaiyar T, Flury P, Krüger N, Su H, Schäkel L, Da Silva EB. et al. Small-Molecule Thioesters as SARS-CoV-2 Main Protease Inhibitors: Enzyme Inhibition, Structure-Activity Relationships, Antiviral Activity, and X-ray Structure Determination. J Med Chem. 2022;65:9376–95. https://doi.org/10.1021/acs.jmedchem.2c00636.

    Article  CAS  PubMed  Google Scholar 

  50. Santos LH, Kronenberger T, Almeida RG, Silva EB, Rocha REO, Oliveira JC. et al. Structure-based identification of naphthoquinones and derivatives as novel inhibitors of main protease Mpro and papain-like protease PLpro of SARS-CoV-2. J Chem Inf Model. 2022;62:6553–73. https://doi.org/10.1021/acs.jcim.2c00693.

    Article  CAS  PubMed  Google Scholar 

  51. Ashhurst AS, Tang AH, Fajtová P, Yoon MC, Aggarwal A, Bedding MJ. et al. Potent Anti-SARS-CoV-2 Activity by the Natural Product Gallinamide A and Analogues via Inhibition of Cathepsin L. J Med Chem. 2022;65:2956–70. https://doi.org/10.1021/acs.jmedchem.1c01494.

    Article  CAS  PubMed  Google Scholar 

  52. Gaulton A, Herse A, Nowotka M, Bento P, Chambers J, Mendez D. et al. The ChEMBL database in 2017. Nucleic Acids Res. 2017;45:D945–D954. https://doi.org/10.1093/nar/gkw1074.

    Article  CAS  PubMed  Google Scholar 

  53. Landrum G. Rdkit documentation. Release. 2013;1:4.

    Google Scholar 

  54. Cereto-Massagué A, Ojeda MJ, Valls C, Mulero M, Garcia-Vallvé S, Pujadas G. Molecular fingerprint similarity search in virtual screening. Methods. 2015;71:58–63. https://doi.org/10.1016/j.ymeth.2014.08.005

    Article  CAS  PubMed  Google Scholar 

  55. Berthold MR, Cebron N, Dill F, Gabriel TR, Kötter T, Meinl T, et al. Wiswedel. KNIME-the Konstanz information miner: version 2.0 and beyond. AcM SIGKDD explorations. Newsletter. 2009;11:26–31.

    Google Scholar 

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Acknowledgements

The authors thank the Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for financial support (CAPES grant numbers 88887.595578/2020-00 and 88887.684031/2022-00 for M.S.M.S fellowship). JGCdR received CNPq grant (No 407779/2021-3). SARS-CoV-2 was isolated from a patient with COVID-19 in São Paulo, Brazil, and was kindly provided by Dr. Edison Durigon, from the Departamento de Microbiologia of Instituto de Ciências Biomédicas of Universidade de São Paulo (USP), Brazil. This virus was obtained by REDE VIRUS (MCTI/Brazil).

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Authors and Affiliations

  1. Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, 31270-901, Minas Gerais, Brazil

    Marina Mol S. A. Verzola, Vinícius Gonçalves Maltarollo & Renata Barbosa de Oliveira

  2. Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, 31270-901, Minas Gerais, Brazil

    Daisymara Priscila de Almeida Marques, Mateus Sá Magalhães Serafim & Jordana Grazziela Alves Coelho-dos-Reis

  3. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0657, USA

    Elany Barbosa da Silva, Mateus Sá Magalhães Serafim, Pavla Fajtová & Anthony John O’Donoghue

  4. Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, 31270-901, Minas Gerais, Brazil

    Rafaela Salgado Ferreira

  5. Chemistry of Natural Bioactive Products, René Rachou Institute - FIOCRUZ Minas, Belo Horizonte, 30190-009, Minas Gerais, Brazil

    Markus Kohlhoff

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Verzola, M.M.S.A., de Almeida Marques, D.P., da Silva, E.B. et al. Synthesis of indole-based ferulic acid derivatives and in vitro evaluation of antiviral activity against SARS-CoV-2. Med Chem Res 32, 2256–2267 (2023). https://doi.org/10.1007/s00044-023-03134-7

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