Skip to main content
SpringerLink
Log in

New vitamin K3 (menadione) analogues: synthesis, characterization, antioxidant and catalase inhibition activities

  • Regular Article
  • Published:
Journal of Chemical Sciences Aims and scope Submit manuscript

Abstract

In this study, derivatives of new vitamin K3 were synthesized by the reactions of 2-methyl-1,4-naphthoquinone 1 with some heterocyclic ring substituted nucleophiles: 1-piperonylpiperazine 2, 1-(2-furoyl)piperazine 5, 1-(2-aminoethyl)piperidine 8, 1-(2-aminoethyl)pyrrolidine 10 and 2,6-dimethyl morpholine 12 in chloroform/triethylamine (TEA) or ethanol at room temperature. Their structures were characterized by Fourier transform infrared spectroscopy (FT-IR), 1H nuclear magnetic resonance (1H NMR), attached proton test nuclear magnetic resonance (APT-NMR) and mass spectrometry (MS). Newly synthesized vitamin K3 derivatives (3, 4, 6, 7, 9, 11, 13, 14) have shown catalase inhibition activity and compound 13 has displayed remarkable potency against catalase enzyme. These compounds were also tested for their antioxidant capacity in vitro by CUPRAC method.

Graphic abstract

New vitamin K3 (menadione) analogues.

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

Figure 1
Scheme 1
Scheme 2
Figure 2

Similar content being viewed by others

References

  1. Kayashima T, Mori M, Yoshida H, Mizushina Y and Matsubara K 2009 1,4-Naphthoquinone is a potent inhibitor of human cancer cell growth and angiogenesis Cancer Lett. 278 34

  2. Prescott B 1969 Potential antimalarial agents. Derivatives of 2-chloro-1,4-naphthoquinone J. Med. Chem. 12 181

  3. Belorgey D, Lanfranchi D A and Davioud-Charvet E 20131,4-Naphthoquinones and other NADPH-dependent glutathione reductase-catalyzed redox cyclers as antimalarial agents Curr. Pharm. Design. 19 2512

  4. Matsumoto K, Choshi T, Hourai M, Zamami Y, Sasaki K, Abe T, Ishikura M, Hatae N, Iwamura T, Tohyama S, Nobuhiro J and Hibino S 2012 Synthesis and antimalarial activity of calothrixins A and B, and their N-alkyl derivatives Bio. Med. Chem. Lett. 22 4762

    Article  CAS  Google Scholar 

  5. Kurban S, Deniz N G, Sayil C, Ozyurek M, Guçlu K, Stasevych M V, et al. 2019 Synthesis, antimicrobial properties, and inhibition of catalase activity of 1,4-naphtho- and benzoquinone derivatives containing N-, S-, O-substituted Heteroatom Chem. 2019 1

    Article  Google Scholar 

  6. Tandon V K, Maurya H K, Mishra N N and Shukla P K 2011 Micelles catalyzed chemoselective synthesis ‘in water’ and biological evaluation of oxygen containing hetero-1,4-naphthoquinones as potential antifungal agents Bio. Med. Chem. Lett. 21 6398

    Article  CAS  Google Scholar 

  7. Ryu C K, Lee J Y, Jeong S H and Nho J H 2009 Synthesis and antifungal activity of 1H-pyrrolo[3,2-g]quinoline-4,9-diones and 4,9-dioxo-4,9-dihydro-1H-benzo[f]indoles Bio. Med. Chem. Lett. 19 146

    Article  CAS  Google Scholar 

  8. Castro M A, Gamito A M and Tangarife-Castano V 2013 Synthesis and antifungal activity of terpenyl-1,4-naphthoquinone and 1,4-anthracenedione derivatives Eur. J. Med. Chem. 67 19

    Article  CAS  Google Scholar 

  9. Jordao A K, Novais J and Leal B 2013 Synthesis using microwave irradiation and antibacterial evaluation of new N,O-acetals and N,S-acetals derived from 2-amino-1,4-naphthoquinones Eur. J. Med. Chem. 63 196

    Article  CAS  Google Scholar 

  10. Deniz N G, Ozyurek, M, Tufan A N and Apak M R 2015 One-pot synthesis, characterization, antioxidant capacity of sulfur and oxygen substituted 1,4-naphthoquinones and a structural study Monatsh. Chem. 146 2117

    CAS  Google Scholar 

  11. Tandon V K, Maurya H K, Verma M K, Kumar R and Shukla P K 2010 On water assisted synthesis and biological evaluation of nitrogen and sulfur containing hetero-1,4-naphthoquinones as potent antifungal and antibacterial agents Eur. J. Med. Chem. 45 2418

    Article  CAS  Google Scholar 

  12. Ryu C K and Kim D H 1992 The synthesis and antimicrobial activities of some 1,4-naphthoquinones (II) Arch. Pharm. Res. 15 263

    CAS  Google Scholar 

  13. Kacmaz A, Deniz N G, Aydinli S G, Sayil C, Onay Ucar E, Mertoglu E, et al. 2019 Synthesis and antiproliferative evaluation of some 1,4-naphthoquinone derivatives against human cervical cancer cells Open Chem. 17 337

  14. Tip-Pyang S, Limpipatwattana Y, Khumkratok S, Siripong P and Sichaem J 2010 A new cytotoxic 1-azaanthraquinone from the stems of Goniothalamus laoticus Fitoterapia 81 894

  15. Huang L J, Chang F C, Lee K H, Wang J P, Teng C M and Kuo S C 1998 Synthesis and antiplatelet, antiinflammatory, and antiallergic activities of substituted 3-chloro-5,8-dimethoxy-1,4-naphthoquinone and related compounds Bio. Med. Chem. 6 2261

    CAS  Google Scholar 

  16. Huang L J, Lien J C, Lee K H, Wang J P, Teng C M and Kuo S C 1996 Synthesis and antiplatelet, antiinflammatory and antiallergic activities of 2,3-disubstituted-1,4-naphthoquinones Chem. Pharm. Bull. 44 1181

    Article  Google Scholar 

  17. Tudor G, Gutierrez P, Aguilera-Gutierrez A and Sausville E A 2003 Cytotoxicity and apoptosis of benzoquinones: redox cycling, cytochrome c release, and BAD protein expression Biochem. Pharm. 65 1061

    CAS  Google Scholar 

  18. Bingol G 1977 Vitamins and Enzymes (Ankara University: Faculty of Pharmacy Publications) p. 46

  19. Berkheij M, Sluis L, Sewing C, Boer D J, Terpstra J W, Hiemstra H, Bakker W I I, Hoogenband A and Maarseveena J H 2005 Synthesis of 2-substituted piperazines via direct α-lithiation Tetrahedron Lett. 46 2369

  20. Vendemiale G, Grattagliano I and Altomare E 1999 An update on the role of free radicals and antioxidant defense in human disease Int. J. Clin. Lab. Res. 29 49

    Article  CAS  Google Scholar 

  21. Apak R, Guclu K, Ozyurek M and Karademir S E 2004 Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neocuproine: CUPRAC method J. Agric. Food. Chem. 52 7970

    Article  CAS  Google Scholar 

  22. Bekdeser B, Ozyurek M, Guclu K, Ustun Alkan F and Apak R 2014 Development of a new catalase activity assay for biological samples using optical CUPRAC sensor Spectrochim. Acta Part A 132 485

    Article  CAS  Google Scholar 

  23. Cameron D W and Scott P M 1964 Facile loss of C-methyl groups during the amination of quinones J. Chem. Soc. 1066 5569

    Article  Google Scholar 

  24. Ohta S, Hinata Y, Yamashita, M and Kawasaki I 1994 One step synthesis of 1,2,3,4-Tetrahydrobenzo[g]quinazoline-5,10-dione derivatives from Vitamin K3 Chem. Pharm. Bull. 42 1730

    Article  CAS  Google Scholar 

  25. Krych J and Gebicka L 2013 Catalase is inhibited by flavonoids Int. J. Biol. Macromol. 58 148

    Article  CAS  Google Scholar 

  26. Chung S-H, Chung S-M, Lee J-Y, Kim S-R, Park K-S and Chung J-H 1999 The biological significance of non-enzymatic reaction of menadione with plasma thiols: enhancement of menadione-induced cytotoxicity to platelets by the presence of blood plasma FEBS Letts. 449 235

    CAS  Google Scholar 

  27. Wefers H and Sies H 1983 Hepatic low-level chemiluminescence during redox cycling of menadione and the menadione-glutathione conjugate: Relation to glutathione and NAD(P)H:quinone reductase (DT-diaphorase) activity Arch. Biochem. Biophys. 224 568

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We gratefully thank the Research Fund of Istanbul University-Cerrahpasa for financial support of this work (Project Numbers: FDK-2017-24871, FBA-2019-30472, FBA-2019-32783).

Author information

Authors and Affiliations

  1. Engineering Faculty, Department of Chemistry, Division of Organic Chemistry, Istanbul University-Cerrahpasa, 34320, Avcilar, Istanbul, Turkey

    NAHIDE GULSAH DENIZ, AESHA F SH ABDASSALAM & CIGDEM SAYIL

  2. Engineering Faculty, Department of Chemistry, Division of Analytical Chemistry, Istanbul University-Cerrahpasa, 34320, Avcilar, Istanbul, Turkey

    MUSTAFA OZYUREK

  3. Vocational School, Polymer Technology Programme, Istanbul Gedik University, Pendik, Istanbul, Turkey

    EMIN AHMET YESIL

Authors
  1. NAHIDE GULSAH DENIZ
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. AESHA F SH ABDASSALAM
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. MUSTAFA OZYUREK
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. EMIN AHMET YESIL
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. CIGDEM SAYIL
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to CIGDEM SAYIL.

Ethics declarations

Conflict of interest

No potential conflict of interest was reported by the authors.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 2323 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

DENIZ, N.G., ABDASSALAM, A.F.S., OZYUREK, M. et al. New vitamin K3 (menadione) analogues: synthesis, characterization, antioxidant and catalase inhibition activities. J Chem Sci 132, 138 (2020). https://doi.org/10.1007/s12039-020-01835-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12039-020-01835-9

Keywords

Search

Navigation