Skip to main content

Advertisement

SpringerLink
Log in

4H-benzochromene derivatives as novel tyrosinase inhibitors and radical scavengers: synthesis, biological evaluation, and molecular docking analysis

  • Original Article
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

A series of ethyl 2-amino-4H-benzo[h]chromene-3-carboxylate derivatives, having phenyl ring with diverse substituents at C4 position of 4H-benzochromene nucleus, were synthesized via one-pot three-component reaction between various aromatic aldehydes, α-naphthol, and ethyl cyanoacetate. The synthesized compounds were screened for their antityrosinase activity. Compound 4i, bearing 4-dimethylamino substitution on C4-phenyl ring, was the most potent tyrosinase inhibitor (IC50 = 34.12 μM). The inhibition kinetic analysis of 4i indicated that the compound was a competitive tyrosinase inhibitor. Compounds 4a, 4g, 4i and 4j were the effective radical scavengers with EC50s in the range of 0.144–0.943 mM. According to the in silico drug-like and ADME predictions, 4i can be considered as a suitable candidate. Molecular docking results confirmed that the derivative was well accommodated within the mushroom tyrosinase binding site. Therefore, 4i can be introduced as a novel tyrosinase inhibitor that might be a promising lead in medicine, cosmetics, and food industry.

Graphic abstract

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
Scheme 1
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Seo S-Y, Sharma VK, Sharma N (2003) Mushroom tyrosinase: recent prospects. J Agric Food Chem 51:2837–2853

    Article  CAS  Google Scholar 

  2. Casanola-Martin GM, Le-Thi-Thu H, Marrero-Ponce Y, Castillo-Garit JA, Torrens F et al (2014) Tyrosinase enzyme: 1. An overview on a pharmacological target. Curr Top Med Chem 14:1494–1501

    Article  CAS  Google Scholar 

  3. Masum MN, Yamauchi K, Mitsunaga T (2019) Tyrosinase inhibitors from natural and synthetic sources as skin-lightening agents. Rev Agric Sci 7:41–58

    Article  Google Scholar 

  4. Greggio E, Bergantino E, Carter D, Ahmad R, Costin GE et al (2005) Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson’s disease. J Neurochem 93:246–256

    Article  CAS  Google Scholar 

  5. Carballo-Carbajal I, Laguna A, Romero-Giménez J, Cuadros T, Bové J et al (2019) Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis. Nat Commun 10:973

    Article  Google Scholar 

  6. Lee SY, Baek N, Nam T-g (2016) Natural, semisynthetic and synthetic tyrosinase inhibitors. J Enzyme Inhib Med Chem 31:1–13

    Article  CAS  Google Scholar 

  7. Chiari ME, Vera DMA, Palacios SM, Carpinella MC (2011) Tyrosinase inhibitory activity of a 6-isoprenoid-substituted flavanone isolated from Dalea elegans. Bioorg Med Chem 19:3474–3482

    Article  CAS  Google Scholar 

  8. Karioti A, Protopappa A, Megoulas N, Skaltsa H (2007) Identification of tyrosinase inhibitors from Marrubium velutinum and Marrubium cylleneum. Bioorg Med Chem 15:2708–2714

    Article  CAS  Google Scholar 

  9. Zolghadri S, Bahrami A, Hassan Khan MT, Munoz-Munoz J, Garcia-Molina F et al (2019) A comprehensive review on tyrosinase inhibitors. J Enzyme Inhib Med Chem 34:279–309

    Article  CAS  Google Scholar 

  10. Ellis GP (2009) Chromenes, chromanones, and chromones. Wiley, Hoboken

    Google Scholar 

  11. Pratap R, Ram VJ (2014) Natural and synthetic chromenes, fused chromenes, and versatility of dihydrobenzo[h]chromenes in organic synthesis. Chem Rev 114:10476–10526

    Article  CAS  Google Scholar 

  12. Sharma K, Kumar S, Chand K, Kathuria A, Gupta A et al (2011) An update on natural occurrence and biological activity of chromones. Curr Med Chem 18:3825–3852

    Article  CAS  Google Scholar 

  13. Emami S, Ghanbarimasir Z (2015) Recent advances of chroman-4-one derivatives: synthetic approaches and bioactivities. Eur J Med Chem 93:539–563

    Article  CAS  Google Scholar 

  14. Keri RS, Budagumpi S, Pai RK, Balakrishna RG (2014) Chromones as a privileged scaffold in drug discovery: a review. Eur J Med Chem 78:340–374

    Article  CAS  Google Scholar 

  15. Patil SA, Patil R, Pfeffer LM, Miller DD (2013) Chromenes: potential new chemotherapeutic agents for cancer. Future Med Chem 5:1647–1660

    Article  CAS  Google Scholar 

  16. Abu-Hashem AA, El-Shazly M (2015) Synthesis, reactions and biological activities of furochromones: a review. Eur J Med Chem 90:633–665

    Article  CAS  Google Scholar 

  17. Ramdani LH, Talhi O, Decombat C, Vermerie M, Berry A et al (2019) Bis (4-hydroxy-2H-chromen-2-one) coumarin induces apoptosis in MCF-7 human breast cancer cells through aromatase inhibition. Anticancer Res 39:6107–6114

    Article  CAS  Google Scholar 

  18. Alblewi FF, Okasha RM, Hritani ZM, Mohamed HM, El-Nassag MA et al (2019) Antiproliferative effect, cell cycle arrest and apoptosis generation of novel synthesized anticancer heterocyclic derivatives based 4H-benzo[h]chromene. Bioorg Chem 87:560–571

    Article  CAS  Google Scholar 

  19. Morimura K, Yamazaki C, Hattori Y, Makabe H, Kamo T et al (2007) A tyrosinase inhibitor, Daedalin A, from mycelial culture of Daedalea dickinsii. Biosci Biotechnol Biochem 71:70266-1–70266-4

    Article  Google Scholar 

  20. Hu X, Wu J-W, Wang M, Yu M-H, Zhao Q-S et al (2011) 2-Arylbenzofuran, flavonoid, and tyrosinase inhibitory constituents of Morus yunnanensis. J Nat Prod 75:82–87

    Article  Google Scholar 

  21. Peralta MA, Ortega MG, Agnese AM, Cabrera JL (2011) Prenylated flavanones with anti-tyrosinase activity from Dalea boliviana. J Nat Prod 74:158–162

    Article  CAS  Google Scholar 

  22. Şöhretoğlu D, Sari S, Barut B, Özel A (2018) Tyrosinase inhibition by some flavonoids: inhibitory activity, mechanism by in vitro and in silico studies. Bioorg Chem 81:168–174

    Article  Google Scholar 

  23. Lee NK, Son KH, Chang HW, Kang SS, Park H et al (2004) Prenylated flavonoids as tyrosinase inhibitors. Arch Pharm Res 27:1132–1135

    Article  CAS  Google Scholar 

  24. Kim SJ, Son KH, Chang HW, Kang SS, Kim HP (2003) Tyrosinase inhibitory prenylated flavonoids from Sophora flavescens. Biol Pharm Bull 26:1348–1350

    Article  CAS  Google Scholar 

  25. Kishore N, Twilley D, Blom van Staden A, Verma P, Singh B et al (2018) Isolation of flavonoids and flavonoid glycosides from Myrsine africana and their inhibitory activities against mushroom tyrosinase. J Nat Prod 81:49–56

    Article  CAS  Google Scholar 

  26. Yu L (2003) Inhibitory effects of (S)-and (R)-6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic acids on tyrosinase activity. J Agric Food Chem 51:2344–2347

    Article  CAS  Google Scholar 

  27. Sabitha G, Bhikshapathi M, Nayak S, Srinivas R, Yadav J (2011) Triton B catalyzed three-component, one-pot synthesis of 2-amino-2-chromenes at ambient temperature. J Heterocycl Chem 48:267–271

    Article  CAS  Google Scholar 

  28. Khurana JM, Nand B, Saluja P (2010) DBU: a highly efficient catalyst for one-pot synthesis of substituted 3, 4-dihydropyrano [3, 2-c] chromenes, dihydropyrano [4, 3-b] pyranes, 2-amino-4H-benzo[h]chromenes and 2-amino-4H benzo[g]chromenes in aqueous medium. Tetrahedron 66:5637–5641

    Article  CAS  Google Scholar 

  29. Chaker A, Najahi E, Nepveu F, Chanchoub F (2017) Microwave-assisted synthesis of chromeno [2, 3-d] pyrimidinone derivatives. Arab J Chem 10:S3040–S3047

    Article  CAS  Google Scholar 

  30. Ha Young Mi, Chung Sang Woon, Song Suhee, Lee Hyojin, Suh Hongsuk et al (2007) 4-(6-Hydroxy-2-naphthyl)-1,3-bezendiol: a potent, new tyrosinase inhibitor. Biol Pharm Bull 30:1711–1715

    Article  CAS  Google Scholar 

  31. Ranjbar S, Akbari A, Edraki N, Khoshneviszadeh M, Hemmatian H et al (2018) 6-Methoxy-3, 4-dihydronaphthalenone chalcone-like derivatives as potent tyrosinase inhibitors and radical scavengers. Lett Drug Des Discov 15:1170–1179

    Article  CAS  Google Scholar 

  32. Tehrani MB, Emani P, Rezaei Z, Khoshneviszadeh M, Ebrahimi M et al (2019) Phthalimide-1, 2, 3-triazole hybrid compounds as tyrosinase inhibitors; synthesis, biological evaluation and molecular docking analysis. J Mol Struct 1176:86–93

    Article  CAS  Google Scholar 

  33. Dehghani Z, Khoshneviszadeh M, Khoshneviszadeh M, Ranjbar S (2019) Veratric acid derivatives containing benzylidene-hydrazine moieties as promising tyrosinase inhibitors and free radical scavengers. Bioorg Med Chem 27:2644–2645

    Article  CAS  Google Scholar 

  34. Mahdavi M, Ashtari A, Khoshneviszadeh M, Ranjbar S, Dehghani A et al (2018) Synthesis of new benzimidazole-1, 2, 3-triazole hybrids as tyrosinase inhibitors. Chem Biodivers 15:e1800120

    Article  Google Scholar 

  35. Ghafari S, Ranjbar S, Larijani B, Amini M, Biglar M et al (2019) Novel morpholine containing cinnamoyl amides as potent tyrosinase inhibitors. Int J Biol Macromol 135:978–985

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Vice-Chancellor for Research, Shiraz University of Medical Sciences with Grant No. 95-01-103-12178. The authors wish to thank Mr. H. Argasi at the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for his invaluable assistance in editing this manuscript.

Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Somaye Karimian, Mahsa Dadfar, Maryam Gholampour, Amirhossein Sakhteman & Mehdi Khoshneviszadeh

  2. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Sara Ranjbar

  3. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Mahsima Khoshneviszadeh & Mehdi Khoshneviszadeh

Authors
  1. Somaye Karimian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sara Ranjbar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahsa Dadfar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mahsima Khoshneviszadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maryam Gholampour
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Amirhossein Sakhteman
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mehdi Khoshneviszadeh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mehdi Khoshneviszadeh.

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.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Karimian, S., Ranjbar, S., Dadfar, M. et al. 4H-benzochromene derivatives as novel tyrosinase inhibitors and radical scavengers: synthesis, biological evaluation, and molecular docking analysis. Mol Divers 25, 2339–2349 (2021). https://doi.org/10.1007/s11030-020-10123-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-020-10123-0

Keywords

Search

Navigation