Synthesis, radical scavenging, and antioxidant activity of stilbazolic resveratrol analogs

Abstract

To continue the research on the preparation of resveratrol structural analogs containing the 3-pyridinol fragment, a series of derivatives with an ethyl radical sterically shielding the hydroxyl group was synthesized. It was shown that the ethyl group introduction has an ambiguous effect on the radical scavenging and antioxidant properties of the stilbazoles studied, which is probably related to the structural features of the resulting radical intermediates. The correlation between the radical scavenging and antioxidant properties of the derivatives studied is established. A number of compounds have been identified that exhibit an antioxidant effect on the mitochondrial membranes lipid peroxidation model, better than the natural prototype and 2-ethyl-6-methylpyridin-3-ol with a related structure used in clinical practice.

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

Fig. 1
Scheme 1
Fig. 2
Scheme 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. Berman AY, Motechin RA, Wiesenfeld MY, Holz MK (2017) The therapeutic potential of resveratrol: a review of clinical trials. NPJ Precis Oncol 1:35

    Article  Google Scholar 

  2. Bhatti JS, Bhatti GK, Reddy PH (2017) Mitochondrial dysfunction and oxidative stress in metabolic disorders—a step towards mitochondria based therapeutic strategies. Biochim Biophys Acta 1863:1066–1077

    CAS  Article  Google Scholar 

  3. Bonnefont-Rousselot D (2016) Resveratrol and cardiovascular diseases. Nutrients 8:250–273

    Article  Google Scholar 

  4. Chesnokova NB, Beznos OV, Pavlenko TA, Zabozlaev AA, Pavlova MV (2015) Effects of hydroxypyridine derivatives mexidol and emoxypin on the reparative processes in rabbit eye on the models of corneal epithelial defect and conjunctival ischemia. Bull Exp Biol Med 158:346–348

    CAS  Article  Google Scholar 

  5. Corcelli A, Saponetti MS, Zaccagnino P, Lopalco P, Mastrodonato M, Liquori GE, Lorusso M (2010) Mitochondria isolated in nearly isotonic KCl buffer: focus on cardiolipin and organelle morphology. Biochim Biophys Acta 1798:681–687

    CAS  Article  Google Scholar 

  6. Daina A, Zoete V (2016) A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem 11:1117–1121

    CAS  Article  Google Scholar 

  7. Devasagayam TPA, Pushpendran CK, Eapen J (1983) Differences in lipid peroxidation of rat liver rough and smooth microsomes. Biochim Biophys Acta 750:91–97

    CAS  Article  Google Scholar 

  8. Egan WJ, Merz Jr. KM, Baldwin JJ (2000) Prediction of drug absorption using multivariate statistics. J Med Chem 43:3867–3877

    CAS  Article  Google Scholar 

  9. Elimadi A, Bouillot L, Sapena R, Tillement J-P, Morin D (1998) Dose-related inversion of cinnarizine and flunarizine effects on mitochondrial permeability transition. Eur J Pharm 348:115–121

    CAS  Article  Google Scholar 

  10. Ertl P, Rohde B, Selzer P (2000) Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem 43:3714–3717

    CAS  Article  Google Scholar 

  11. Fauconneau B, Waffo-Teguo P, Huguet F, Barrier L, Decendit A, Merillon J-M (1997) Comparative study of radical scavenger and antioxidant properties of phenolic compounds from vitis vinifera cell cultures using in vitro tests. Life Sci 61:2103–2110

    CAS  Article  Google Scholar 

  12. Garipov MR, Strelnik AD, Shtyrlin NV, Nagimova AI, Naumov AK, Morozov OA, Balakin KV, Shtyrlin YG (2018) Synthesis and nonlinear optical properties of pyridoxine-based stilbazole derivatives and their azo-analogs. Synth Commun 48:768–777

    CAS  Article  Google Scholar 

  13. Gülçin I (2010) Antioxidant properties of resveratrol: a structure-activity insight. Innov Food Sci Emerg Technol 11:210–218

    Article  Google Scholar 

  14. He F (2011) Bradford protein assay. Bio 101:e45

    Google Scholar 

  15. Indo HP, Yen H-C, Nakanishi I, Matsumoto K, Tamura M, Nagano Y, Matsui H, Gusev O, Cornette R, Okuda T, Minamiyama Y, Ichikawa H, Suenaga S, Oki M, Sato T, Ozawa T, Clair DKS, Majima HJ (2015) A mitochondrial superoxide theory for oxidative stress diseases and aging. J Clin Biochem Nutr 56:1–7

    CAS  Article  Google Scholar 

  16. Jardim FR, de Rossi FT, Nascimento MX, da Silva Barros RG, Borges PA, Prescilio IC, de Oliveira MR (2018) Resveratrol and brain mitochondria: a review. Mol Neurobiol 55:2085–2101

    CAS  Article  Google Scholar 

  17. Khan OS, Bhat AA, Krishnankutty R, Mohammad RM, Uddin S (2016) Therapeutic potential of resveratrol in lymphoid malignancies. Nutr Cancer 68:365–373

    CAS  Article  Google Scholar 

  18. Khanduja KL, Bhardwaj A (2003) Stable free radical scavenging and antiperoxidative properties of resveratrol compared in vitro with some other bioflavonoids. Indian J Biochem Biophys 40:416–22

    CAS  PubMed  Google Scholar 

  19. Li Q-S, Li Y, Deora GS, Ruan B-F (2019) Derivatives and analogues of resveratrol: recent advances in structural modification. Mini-Rev Medicinal Chem 19:809–825

    CAS  Article  Google Scholar 

  20. Markus MA, Morris BJ (2008) Resveratrol in prevention and treatment of common clinical conditions of aging. Clin Inter Aging 3:331–339

    CAS  Google Scholar 

  21. Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 97:55–74

    CAS  Article  Google Scholar 

  22. Poulsen MM, Fjeldborg K, Ornstrup MJ, Kjær TN, Nøhr MK, Pedersen SB (2015) Resveratrol and inflammation: Challenges in translating pre-clinical findings to improved patient outcomes. Biochim Biophys Acta 1852:1124–1136

    CAS  Article  Google Scholar 

  23. Ray PD, Huang B-W, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981–990

    CAS  Article  Google Scholar 

  24. Semenov AV, Balakireva OI, Tarasova IV, Burtasov AA, Semenova EV, Petrov PS, Minaeva OV, Pyataev NA (2018) Synthesis, theoretical, and experimental study of radical scavenging activity of 3-pyridinol containing trans-resveratrol analogs. Med Chem Res 27:1298–1308

    CAS  Article  Google Scholar 

  25. Semenov AV, Balakireva OI, Tarasova IV, Semenova EV, Minaeva OV (2019) Spectroscopic properties of some hydroxylated 2-stilbazole derivatives. J Fluoresc 29:1301–1309

    CAS  Article  Google Scholar 

  26. Sies H, Berndt C, Jones DP (2017) Oxidative stress. Annu Rev Biochem 86:715–748

    CAS  Article  Google Scholar 

  27. Singh N, Agrawal M, Doré S (2013) Neuroprotective properties and mechanisms of resveratrol in in vitro and in vivo experimental cerebral stroke models. ACS Chem Neurosci 4:1151–1162

    CAS  Article  Google Scholar 

  28. Wakabayashi S, Kiyohara Y, Kameda S, Uenishi J, Oae S (1990) Ligand coupling of 2-pyridyl sulfoxides having an sp2 stereocenter at the α-position: a novel preparation of α-stilbazoles. Heteroat Chem 1:225–232

    CAS  Article  Google Scholar 

  29. Westphal CH, Dipp MA, Guarente L (2007) A therapeutic role for sirtuins in diseases of aging? Trends Biochem Res 32:555–560

    CAS  Article  Google Scholar 

Download references

Funding

The reported study was funded by RFBR according to the research project No. 18-43-130004.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Alexander V. Semenov.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

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

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Semenov, A.V., Balakireva, O.I., Tarasova, I.V. et al. Synthesis, radical scavenging, and antioxidant activity of stilbazolic resveratrol analogs. Med Chem Res (2020). https://doi.org/10.1007/s00044-020-02585-6

Download citation

Keywords

  • Resveratrol
  • 2-stilbazole
  • 3-pyridinol
  • Antioxidant
  • DPPH
  • MDA