Skip to main content
SpringerLink
Log in

Theoretical insight on antioxidant potency of kanzakiflavone-2 and its derivatives

  • Original Research
  • Published:
Structural Chemistry Aims and scope Submit manuscript

Abstract

Functional groups in flavonoids always act as deciding factors in making a particular flavonoid to be active. They possess the capability to enhance or diminish the structural activity of flavonoids. The idea about conjugated functional units and their role over structural activity alteration still seems to be less explored. In the present work, kanzakiflavone and its derivatives possessing the structural activity directors –OH, -OCH3, and –O-CH2-O- are analyzed using density functional theory with help of global hybrid meta GGA correlation functional (M06-2X) under the basis set 6-311++G(d,p). Energy surface analysis (frontier molecular orbitals and electrostatic potential) based on charge distribution shows that the studied flavonoids prefer to act as potential electron donors. Interestingly, the electron rich area (A-ring) is profound to be altered with B-ring in comparison with other flavones. All the studied flavonoids prefer to act as potential radical scavengers in aqueous phase which is witnessed via antioxidant mechanisms. Absorption, digestion, metabolism, and excretion (ADME) analysis was carried out to understand the nominal role of flavonoids to meet medicinal applications. Kanzakiflavone and its derivatives prefer to act as possible leads based on physiological, pharmacological, and lipophilic properties.

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

Similar content being viewed by others

Data availability

Supplementary information is provided as separate attachment.

References

  1. Kuhnau J (1976) The flavonoids. A class of semi-essential food components: their role in human nutrition. World ReV. Nutr Diet 24:117–191

    CAS  Google Scholar 

  2. Walle T (2004) Absorption and metabolism of flavonoids. Free Radical Biol Med 36:829–837

    Article  CAS  Google Scholar 

  3. Walle T (2007a) Methylation of dietary flavones greatly improves their hepatic metabolic stability and intestinal absorption. Mol Pharm 4:826–832

    Article  CAS  PubMed  Google Scholar 

  4. Walle T (2007b) Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass? Semin Cancer Biol 17:354–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Walle T (2009) Methylation of dietary flavones increases their metabolic stability and chemopreventive effects. Int J Mol Sci 10:5002–5019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Qin MJ, Ji WL, Wang ZT (2004) Studies on the constituents of Belamcanda chinensis (II). Chin Tradit Herb Drugs 35:487–489

    CAS  Google Scholar 

  7. Jianbo Xiao, Xiaoling Ni, Guoyin Kai & Xiaoqing Chen : A review on structure–activity relationship of dietary polyphenols inhibiting α-amylase, Critical Reviews in Food Science and Nutrition, 53:5, 497-506.(2013)

    Google Scholar 

  8. Iinuma M, Tanaka T, Matsuura S (1984) Synthetic studies of the flavone derivatives. VIII. Synthesis of kanzakiflavones and their isomers. Chem Pharm Bull 32(3):1006–1010

    Article  CAS  Google Scholar 

  9. Zhang L, Wei LK, Xu J, Yang D, Zhang C, Wang Z, Li M (2016) Belamcanda chinensis (L.) DC-An ethnopharmacological, phytochemical and pharmacological review. J Ethnopharmacol 186:1–13

    Article  CAS  PubMed  Google Scholar 

  10. Hohenstein EG, Chill ST, Sherrill CD (2008) Assessment of the performance of the M05−2X and M06−2X exchange-correlation functionals for noncovalent interactions in biomolecules. J Chem Theory Comput 4(12):1996–2000. https://doi.org/10.1021/ct800308k

    Article  CAS  PubMed  Google Scholar 

  11. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery Jr JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2009) Gaussian 09, Revision A.02, Gaussian, Inc. , Wallingford CT

  12. Lu T (2012) Feiwu Chen, Multiwfn: a multifunctional wavefunction analyzer. J Comput Chem 33:580–592

    Article  PubMed  Google Scholar 

  13. Leopoldini M, Prieto Pitarch I, Russo N, Toscano M (2004) Structure, conformation, and electronic properties of apigenin, luteolin, and taxifolin antioxidants. A first principle theoretical study. J Phys Chem B 108:92–94

    Article  Google Scholar 

  14. (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7:42717

  15. Csizmadia IG (1976) Theory and practice of MO calculations on organic molecules. Elsevier, Amsterdam

    Google Scholar 

  16. Campion, Gillis, and Oxtoby Principles of modern chemistry6th edn. Thomson Brooks/Cole, Belmont

  17. Politzer P, Laurence PR, Jayasuriya K (1985) Molecular electrostatic potentials: an effective tool for the elucidation of biochemical phenomena. Environ Health Perspect 61:191–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ditchfield R, Hehre WJ, Pople JA (1971) Self-consistent molecular-orbital methods: IX. An extended Gaussian-type basis for molecular-orbital studies of organic molecules. J Chem Phys 54:724–728

    Article  CAS  Google Scholar 

  19. Hehre WJ, Ditchfield R, Pople JA (1972) Self-consistent molecular orbital methods: XII. Further extensions of Gaussian type basis sets for use in molecular orbital studies of organic molecules. J Chem Phys 56:2257–2261

    Article  CAS  Google Scholar 

  20. Reed AE, Curtiss LA, Weinhold F (1988) Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem Rev 88:899–926

    Article  CAS  Google Scholar 

  21. Weinhold F, Carpenter JE (1988) The structure of small molecules and ions. Plenum, New York, pp 227–236

    Book  Google Scholar 

  22. Weinhold F, Landis CR (2012) Discovering chemistry with natural bond orbitals. John Wiley & Sons, New Jersey, pp 132–133

    Book  Google Scholar 

  23. Mulliken RS (1955) Electronic population analysis on LCAO-MO molecular wave functions. I. J Chem Phys 23(10):1833–1840

    Article  CAS  Google Scholar 

  24. Scherer W, Sirsch P, Shorokhov D, Tafipolsky M, McGrady GS, Gullo E (2003) Valence charge concentrations, electron delocalisation and β-agostic bonding in d10 metal alkyl complexes. Chem Eur J 9:6057–6070

    Article  CAS  PubMed  Google Scholar 

  25. Sadasivam K, Kumaresan R (2011) Antioxidant behavior of mearnsetin and myricetin flavonoid compounds—a DFT study. Spectrochim Acta A Mol Biomol Spectrosc 79(1):282–293

    Article  CAS  PubMed  Google Scholar 

  26. Praveena R, Sadasivam K, Kumaresan R, Deepha V, Sivakumar R (2013) Experimental and DFT studies on the antioxidant activity of a C-glycoside from Rhynchosiacapitata. Spectrochim Acta A 103:442–452

    Article  CAS  Google Scholar 

  27. Leopoldini M, Marino T, Russo N, Toscano M (2004) Antioxidant properties of phenolic compounds. H-atom versus electron transfer mechanism. J Phys Chem B 108:4916–4922

    Article  CAS  Google Scholar 

  28. Galano AA, Mazzone G, Alvarez-Diduk R, Marino T, JR Alvarez-Idaboy N (2016) Russo Food antioxidants: chemical insights at the molecular level. Annu Rev Food Sci Technol 7:335–352

    Article  CAS  PubMed  Google Scholar 

  29. Zhang J, Brodbelt JS (2004) Gas-phase hydrogen/deuterium exchange and conformations of deprotonated flavonoids and gas-phase acidities of flavonoids. J Am Chem Soc 126:5906–5919

    Article  CAS  PubMed  Google Scholar 

  30. Parker VD (1992) Homolytic bond (H-A) dissociation free energies in solution. Applications of the standard potential of the (H+/H•) couple. J Am Chem Soc 114(19):7458–7462. https://doi.org/10.1021/ja00045a018

    Article  CAS  Google Scholar 

  31. Bizarro MM, Costa Cabral BJ, Borges Dos Santos RMB, Martinho Simões JA (1999) Substituent effects on the O-H bond dissociation enthalpies in phenolic compounds: agreements and controversies. Pure Appl Chem 71(7):1249–1256. https://doi.org/10.1046/j.1365-3075.1999.00279.x

    Article  CAS  Google Scholar 

  32. Ertl P, Schuffenhauer A (2009) Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. J Chem inform 1:8

    Google Scholar 

  33. Tian S et al (2015) The application of in silico drug-likeness predictions in pharmaceutical research. Adv Drug Deliv Rev 86:2–10

    Article  CAS  PubMed  Google Scholar 

  34. Dahlin JL, Inglese J, Walters MA (2015) Mitigating risk in academic preclinical drug discovery. Nat Rev Drug Discov 14:279–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Arnott JA, Planey SL (2012) The influence of lipophilicity in drug discovery and design. Expert Opin Drug Discovery 7:863–875

    Article  CAS  Google Scholar 

  36. Savjani KT, Gajjar AK, Savjani JK (2012) Drug solubility: importance and enhancement techniques. ISRN Pharm 2012:195727

    PubMed  PubMed Central  Google Scholar 

  37. Potts RO, Guy RH (1992) Predicting skin permeability. Pharm Res 09:663–669

    Article  CAS  Google Scholar 

  38. Wolf CR, Smith G, Smith RL (2000) Pharmacogenetics. Br Med J

  39. Ghose AK, Viswanadhan VN, Wendoloski JJ (1999) A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. J Comb Chem 1:55–68

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The authors acknowledge the Science and Engineering Research Board, Department of Science and Technology (DST-SERB), Government of India, for funding through the research grant (EMR/2016/002892).

Author information

Authors and Affiliations

  1. Quantum Computing and Phytochemistry Research Laboratory, Bannari Amman Institute of Technology, Sathyamangalam, Tamil Nadu, 638 401, India

    K. Anbazhakan, R. Praveena & K. Sadasivam

  2. Department of Chemistry, Bannari Amman Institute of Technology, Sathyamangalam, Tamil Nadu, 638 401, India

    K. Anbazhakan & R. Praveena

  3. Department of Physics, Bannari Amman Institute of Technology, Sathyamangalam, Tamil Nadu, 638 401, India

    K. Sadasivam

Authors
  1. K. Anbazhakan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Praveena
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Sadasivam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Praveena.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Code availability

Not applicable

Additional information

Publisher’s note

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

Supplementary Information

ESM 1

(DOC 372 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Anbazhakan, K., Praveena, R. & Sadasivam, K. Theoretical insight on antioxidant potency of kanzakiflavone-2 and its derivatives. Struct Chem 32, 1451–1458 (2021). https://doi.org/10.1007/s11224-020-01722-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11224-020-01722-6

Keywords

Search

Navigation