Skip to main content
SpringerLink
Log in

Antioxidant capacity of simplified oxygen heterocycles and proposed derivatives by theoretical calculations

  • Original Paper
  • Published:
Journal of Molecular Modeling Aims and scope Submit manuscript

Abstract

Context

Some structural properties can be involved in the antioxidant capacity of several polyphenol derivatives, among them their simplified structures. This study examines the contribution of simplified structure for the antioxidant capacity of some natural and synthetic antioxidants. The resonance structures were related to the π-type electron system of carbon-carbon double bonds between both phenyl rings. Trans-resveratrol, phenyl-benzofuran, phenyl-indenone, and benzylidene-benzofuranone are the best basic antioxidant templates among the simplified derivatives studied here. Additionally, the stilbene moiety was found on the molecules with the best antioxidant capacity. Furthermore, our investigation suggests that these compounds can be used as antioxidant scaffold for designing and developing of new promising derivatives.

Methods

To investigate the structure–antioxidant capacity for sixteen simplified natural and proposed derivatives we have employed density functional theory and used Gaussian 09. Our DFT calculations were performed using the B3LYP functional and the 6-31+G(d,p) basis set. All electron transfer mechanisms were investigated by using values of HOMO, ionization potential, energy affinity, stabilization energies, and spin density distributions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Data availability

Not applicable.

Code availability

Gaussian 09 software code G9S016832734579W-5269 N.

References

  1. De S, Aamna B, Sahu R, Parida S, Behera SK, Dan AK (2022) Seeking heterocyclic scaffolds as antivirals against dengue virus. Eur J Med Chem 240:114576. https://doi.org/10.1016/j.ejmech.2022.114576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Haider K, Haider MR, Neha K, Yar MS (2020) Free radical scavengers: An overview on heterocyclic advances and medicinal prospects. Eur J Med Chem 204:112607. https://doi.org/10.1016/j.ejmech.2020.112607

    Article  CAS  PubMed  Google Scholar 

  3. Matos MJ, Vazquez-Rodriguez S, Fonseca A, Uriarte E, Santana L, Borges F (2017) Heterocyclic antioxidants in nature: coumarins. Curr Org Chem 21(4):311–324. https://doi.org/10.2174/1385272820666161017170652

    Article  CAS  Google Scholar 

  4. Jeremić S, Amić A, Stanojević-Pirković M, Marković Z (2018) Selected anthraquinones as potential free radical scavengers and P-glycoprotein inhibitors. Org Biomol Chem 16(11):1890–1902. https://doi.org/10.1039/C8OB00060C

    Article  PubMed  Google Scholar 

  5. Weisburger JH (1999) Mechanisms of action of antioxidants as exemplified in vegetables, tomatoes and tea. Food Chem Toxicol 37(9-10):943–948. https://doi.org/10.1016/s0278-6915(99)00086-1

    Article  CAS  PubMed  Google Scholar 

  6. Sui G, Li T, Zhang B, Wang R, Hao H, Zhou W (2021) Recent advances on synthesis and biological activities of aurones. Bioorg Med Chem 1(29):115895. https://doi.org/10.1016/j.bmc.2020.115895

    Article  CAS  Google Scholar 

  7. Panda SS, Chand M, Sakhuja R, Jain SC (2013) Xanthones as potential antioxidants. Curr Med Chem 20(36):4481–4507. https://doi.org/10.2174/09298673113209990144

    Article  CAS  PubMed  Google Scholar 

  8. Matos MJ, Mura F, Vazquez-Rodriguez S, Borges F, Santana L, Uriarte E, Olea-Azar C (2015) Study of coumarin-resveratrol hybrids as potent antioxidant compounds. Molecules 20(2):3290–3308. https://doi.org/10.3390/molecules20023290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yamagata K, Yamori Y (2020) Inhibition of endothelial dysfunction by dietary flavonoids and preventive effects against cardiovascular disease. J Cardiovasc Pharmacol 75(1):1–9. https://doi.org/10.1097/FJC.0000000000000757

    Article  CAS  PubMed  Google Scholar 

  10. Fang X, Hu X (2018) Advances in the synthesis of lignan natural products. Molecules 23(12):3385. https://doi.org/10.3390/molecules23123385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rajeshwari KC, Hiremathad A, Singh M, Santos MA, Keri RS (2017) A review on antioxidant potential of bioactive heterocycle benzofuran: Natural and synthetic derivatives. Pharmacol Rep 69:281–295. https://doi.org/10.1016/j.pharep.2016.11.007

    Article  CAS  PubMed  Google Scholar 

  12. Thuy PT, Trang NV, Son NT (2020) Antioxidation of 2-phenylbenzofuran derivatives: structural-electronic effects and mechanisms. RSC Advances 10(11):6315–6332. https://doi.org/10.1039/C9RA10835A

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Seery MK, Draper SM, Kelly JM, McCabe T, McMurry TBH (2005) The synthesis, structural characterization and photochemistry of some 3-phenylindenones. Synthesis 3:470–474. https://doi.org/10.1055/s-2005-861799

    Article  CAS  Google Scholar 

  14. Miao Y, Hu Y, Yang J, Liu T, Sun J, Wang X (2019) Natural source, bioactivity and synthesis of benzofuran derivatives. RSC Advances 9(47):27510–27540. https://doi.org/10.1039/C9RA04917G

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Patel S, Rathod B, Regu S, Chak S, Shard A (2020) A perspective on synthesis and applications of fluorenones. Chem Select 5(34):10673–10691. https://doi.org/10.1002/slct.202002695

    Article  CAS  Google Scholar 

  16. Hayyan M, Hashim MA, AlNashef IM (2016) Superoxide ion: generation and chemical implications. Chem Rev 116(5):3029–3085. https://doi.org/10.1021/acs.chemrev.5b00407

    Article  CAS  PubMed  Google Scholar 

  17. Gulcin İ (2020) Antioxidants and antioxidant methods: an updated overview. Arch Toxicol 94(3):651–715. https://doi.org/10.1007/s00204-020-02689-3

    Article  CAS  PubMed  Google Scholar 

  18. Harjumäki R, Pridgeon CS, Ingelman-Sundberg M (2021) CYP2E1 in alcoholic and non-alcoholic liver injury. Roles of ROS, reactive intermediates and lipid overload. Int J Mol Sci 22(15):8221–8240. https://doi.org/10.3390/ijms22158221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Negre-Salvayre A, Auge N, Ayala V, Basaga H, Boada J, Brenke R, Chapple S, Cohen G, Feher J, Grune T, Lengyel G, Mann GE, Pamplona R, Poli G, Portero-Otin M, Riahi Y, Salvayre R, Sasson S, Serrano J, Shamni O, Siems W, Siow RCM, Wiswedel I, Zarkovic K, Zarkovic N (2010) Pathological aspects of lipid peroxidation. Free Rad Res 44(10):1125–1171. https://doi.org/10.3109/10715762.2010.498478

  20. Albuquerque RV, Malcher NS, Amado LL, Coleman MD, dos Santos DC, Borges RS, Valente SAS, Valente VC, Monteiro MC (2015) In vitro protective effect and antioxidant mechanism of resveratrol induced by dapsone hydroxylamine in human cells. PLoS ONE 10(8):e0134768. https://doi.org/10.1371/journal.pone.0134768

  21. Galano A (2017) Free radicals induced oxidative stress at a molecular level. J Mex Chem Soc 59(4):231–262. https://www.scielo.org.mx/pdf/jmcs/v59n4/v59n4a2.pdf

    Article  Google Scholar 

  22. Han KH, Hashimoto N, Fukushima M (2016) Relationships among alcoholic liver disease, antioxidants, and antioxidant enzymes. World J Gastroent 22(1):37–49. https://doi.org/10.3748/wjg.v22.i1.37

    Article  CAS  Google Scholar 

  23. Kawamura T, Muraoka I (2018) Exercise-induced oxidative stress and the effects of antioxidant intake from a physiological viewpoint. Antioxidants 7(9):119–137. https://doi.org/10.3390/antiox7090119

  24. Huang D, Ou B, Prior RL (2005) The chemistry behind antioxidant capacity assays. J Agric Food Chem 53(6):1841–1856. https://doi.org/10.1021/jf030723c

    Article  CAS  PubMed  Google Scholar 

  25. Santos KLB, Bragança VAN, Pacheco LV, Ota SSB, Aguiar CPP, Borges RS (2022) Essential features for antioxidant capacity of ascorbic acid (vitamin C). J Mol Model 28(1):1–8. https://doi.org/10.1007/s00894-021-04994-9

    Article  CAS  Google Scholar 

  26. Ou-Yang SS, Lu JY, Kong XQ, Liang ZJ, Luo C, Jiang H (2012) Computational drug discovery. Acta Pharmacol Sin 33(9):1131–1140. https://doi.org/10.1038/aps.2012.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lobo V, Patil A, Phatak A, Chandra N (2010) Free radicals, antioxidants and functional foods: Impact on human health. Pharmacog Rev 4(8):118–126. https://doi.org/10.4103/0973-7847.70902

    Article  CAS  Google Scholar 

  28. Palheta IC, Ferreira LR, Vale JKL, Silva OPP, Herculano AM, Oliveira KRHM, Chaves Neto AMJ, Campos JM, Santos CBR, Borges RS (2020) Alkylated sesamol derivatives as potent antioxidants. Molecules 25(14):3300. https://doi.org/10.3390/molecules25143300

    Article  CAS  Google Scholar 

  29. das Neves PAPFG, Lobato CC, Ferreira LR, Bragança VAN, Veiga AAS, Ordoñez ME, Barros VA, de Aguiar CPO, Borges RS (2020) Molecular modification approach on kojic acid derivatives as antioxidants related to ascorbic acid. J Mol Model 26(11):318–326. https://doi.org/10.1007/s00894-020-04580-5

    Article  CAS  PubMed  Google Scholar 

  30. Tsolaki E, Nobelos P, Geronikaki A, Rekka EA (2014) Selected heterocyclic compounds as antioxidants. Synthesis and biological evaluation. Curr Top Med Chem 14(22):2462–2477. https://doi.org/10.2174/1568026614666141203120425

    Article  CAS  PubMed  Google Scholar 

  31. Adelusi TI, Akinbolaji GR, Yin X, Ayinde KS, Olaoba OT (2021) Neurotrophic, anti-neuroinflammatory, and redox balance mechanisms of chalcones. Eur J Pharmacol 15(891):173695. https://doi.org/10.1016/j.ejphar.2020.173695

    Article  CAS  Google Scholar 

  32. Alara OR, Abdurahman NH, Ukaegbu CI (2021) Extraction of phenolic compounds: a review. Curr Res Food Sci 4:200–214. https://doi.org/10.1016/j.crfs.2021.03.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cramer J, Sager CP, Ernst B (2019) Hydroxyl groups in synthetic and natural-product-derived therapeutics: a perspective on a common functional group. J Med Chem 62(20):8915–8930. https://doi.org/10.1021/acs.jmedchem.9b00179

    Article  CAS  PubMed  Google Scholar 

  34. Schaub J, Zielesny A, Steinbeck C, Sorokina M (2020) Too sweet: cheminformatics for deglycosylation in natural products. J Cheminform 12:67. https://doi.org/10.1186/s13321-020-00467-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Guzmán-Ávila R, Avelar M, Márquez EA, Rivera-Leyva JC, Mora JR, Flores-Morales V, Rivera-Islas J (2021) Synthesis, in vitro, and in silico analysis of the antioxidative activity of dapsone imine derivatives. Molecules 26(19):5747. https://doi.org/10.3390/molecules26195747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Charlton NC, Mastyugin M, Török B, Török M (2023) Structural features of small molecule antioxidants and strategic modifications to improve potential bioactivity. Molecules 28(3):1057. https://doi.org/10.3390/molecules28031057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mendes APS, Borges RS, Chaves Neto AMJ, de Macedo LGM, da Silva ABF (2012) The basic antioxidant structure for flavonoid derivatives. J Mol Model 18(9):4073–4080. https://doi.org/10.1007/s00894-012-1397-0

    Article  CAS  PubMed  Google Scholar 

  38. Habgood M, James T, Heifetz A (2020) Conformational searching with quantum mechanic. Methods Mol Biol 2114:207–229. https://doi.org/10.1007/978-1-0716-0282-9_14

    Article  CAS  PubMed  Google Scholar 

  39. Maciel EN, Soares IN, da Silva SC, de Souza GLC (2019) A computational study on the reaction between fisetin and 2,2-diphenyl-1-picrylhydrazyl (DPPH). J Mol Model 25(4):103. https://doi.org/10.1007/s00894-019-3969-8

  40. Nakajima M, Adachi Y, Nemoto T (2022) Publisher Correction: computation-guided asymmetric total syntheses of resveratrol dimers. Nat Communic 13(1):152–161. https://doi.org/10.1038/s41467-022-30160-7

    Article  CAS  Google Scholar 

  41. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Petersson GA, Nakatsuji H, Li X, Caricato M, Marenich A, Bloino J, Janesko BG, Gomperts R, Mennucci B, Hratchian HP, Ortiz JV, Izmaylov AF, Sonnenberg JL, Williams-Young D, Ding F, Lipparini F, Egidi F, Goings J, Peng B, Petrone A, Henderson T, Ranasinghe D, Zakrzewski VG, Gao J, Rega N, Zheng G, Liang W, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Throssell K, Montgomery Jr JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Millam JM, Klene M, Adamo C, Cammi R, Ochterski JW, Martin RL, Morokuma K, Farkas O, Foresman JB, Fox DJ (2016) Gaussian 16, revision C.01. Gaussian, Inc, Wallingford CT

  42. Zhou B, Hu Z, Jiang Y, He X, Sun Z, Sun H (2018) Benchmark study of ionization potentials and electron affinities of armchair single-walled carbon nanotubes using density functional theory. J Phys Cond Mat 30(21):215501–215509. https://doi.org/10.1088/1361-648X/aabd18

    Article  Google Scholar 

  43. Prasad VK, Otero-de-la-Roza A, DiLabio GA (2022) Small-basis set Density-Functional Theory methods corrected with atom-centered potentials. J Chem Theory Comput 18(5):2913–2930. https://doi.org/10.1021/acs.jctc.2c00036

    Article  CAS  PubMed  Google Scholar 

  44. Borges RS, Batista Jr J, Viana RB, Baetas AC, Orestes E, Andrade MA, Honório KM, da Silva ABF (2013) Understanding the molecular aspects of tetrahydrocannabinol and cannabidiol as antioxidants. Molecules 18(10):12663–12674. https://doi.org/10.3390/molecules181012663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Tirado-Rives J, Jorgensen WL (2008) Performance of B3LYP Density Functional methods for a large set of organic molecules. J Chem Theory Comput 4(2):297–306. https://doi.org/10.1021/ct700248k

    Article  CAS  PubMed  Google Scholar 

  46. Yang Y, Ga H (2012) Comparison of DFT methods for molecular structure and vibration spectra of ofloxacin calculations spectrochim. Acta A Mol Biomol Spectrosc. 85(1):303–309. https://doi.org/10.1016/j.saa.2011.10.019

    Article  CAS  Google Scholar 

  47. Zheng YZ, Deng G, Liang Q, Chen DF, Guo R, Lai RC (2017) Antioxidant activity of quercetin and its glucosides from propolis: a theoretical study. Sci Rep 7(1):7543. https://doi.org/10.1038/s41598-017-08024-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Farrokhnia M (2020) Density Functional Theory studies on the antioxidant mechanism and electronic properties of some bioactive marine meroterpenoids: Sargahydroquionic acid and sargachromanol. ACS Omega 5(32):20382–20390. https://doi.org/10.1021/acsomega.0c02354

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Leopoldini M, Rondinelli F, Russo N, Toscano M (2010) Pyranoanthocyanins: a theoretical investigation on their antioxidant activity. J Agric Food Chem 58(15):8862–8871. https://doi.org/10.1021/jf101693k

    Article  CAS  PubMed  Google Scholar 

  50. Yi Y, Adrjan B, Li J, Hu B, Roszak S (2019) NMR studies of daidzein and puerarin: active anti-oxidants in traditional Chinese medicine. J Mol Model 25(7):202. https://doi.org/10.1007/s00894-019-4090-8

    Article  CAS  PubMed  Google Scholar 

  51. Queiroz AN, Martins CC, Santos KLB, Carvalho ES, Owiti AO, Oliveira KRM, Herculano AM, Da Silva ABF, Borges RS (2020) Experimental and theoretical study on structure-tautomerism among edaravone, isoxazolone, and their heterocycles derivatives as antioxidants. Saudi Pharm J 28(7):819–827. https://doi.org/10.1016/j.jsps.2020.06.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Vidhya V, Austine A, Arivazhagan M (2020) Molecular structure, aromaticity, vibrational investigation and dual descriptor for chemical reactivity on 1- chloroisoquinoline using quantum chemical studies. Results in Materials 6:100097. https://doi.org/10.1016/j.rinma.2020.100097

    Article  Google Scholar 

  53. Bentes AL, Borges RS, Monteiro WR, de Macedo LGM, Alves CN (2016) Structure of dihydrochalcones and related derivatives and their scavenging and antioxidant activity against oxygen and nitrogen radical species. Molecules 16(2):1749–1760. https://doi.org/10.3390/molecules16021749

    Article  CAS  Google Scholar 

  54. Queiroz AN, Gomes BAQ, Moraes Jr WM, Borges RS (2009) A theoretical antioxidant pharmacophore for resveratrol. Eur J Med Chem 44(4):1644–1649. https://doi.org/10.1016/j.ejmech.2008.09.023

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors are grateful to CNPq for financial support.

Author information

Authors and Affiliations

  1. Núcleo de Estudos e Seleção de Compostos Bioativos, Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil

    Rosivaldo S. Borges, Christiane P. O. Aguiar, Nicole L. L. Oliveira, Israel N. A. Amaral, Joyce K. L. Vale & Auriekson N. Queiroz

  2. Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, São Carlos, SP, 13560-970, Brazil

    Rosivaldo S. Borges & Albérico B. F. da Silva

  3. Faculdade de Física, Instituto de Ciências Exatas e Naturais, Universidade Federal do Pará, Belém, PA, 66075-110, Brazil

    Antonio M. J. Chaves Neto

Authors
  1. Rosivaldo S. Borges
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christiane P. O. Aguiar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nicole L. L. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Israel N. A. Amaral
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joyce K. L. Vale
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio M. J. Chaves Neto
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Auriekson N. Queiroz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Albérico B. F. da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization, Rosivaldo S. Borges; data extraction, Christiane P. O. Aguiar and Nicole L. L. Oliveira; structure–reactivity, Joyce K. L. Vale; calculations, Israel N. A. Amaral; electronic properties, Antonio M. J. Chaves Neto; editing, Albérico B. F. da Silva; final version, Rosivaldo S. Borges.

Corresponding author

Correspondence to Rosivaldo S. Borges.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Yes.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Borges, R.S., Aguiar, C.P.O., Oliveira, N.L.L. et al. Antioxidant capacity of simplified oxygen heterocycles and proposed derivatives by theoretical calculations. J Mol Model 29, 232 (2023). https://doi.org/10.1007/s00894-023-05602-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00894-023-05602-8

Keywords

Search

Navigation