Structure-activity relationship of dihydroxy-4-methylcoumarins as powerful antioxidants: Correlation between experimental & theoretical data and synergistic effect

Vessela D. Kancheva, Luciano Saso, Petya V. Boranova, Abdullah Khan, Manju K. Saroj, Mukesh Pandey, Shashwat Malhotra, Jordan Z. Nechev, Sunil K. Sharma, Ashok K. Prasad, Maya B. Georgieva, Carleta Joseph, Anthony L. DePass, Ramesh C. Rastogi, Virinder S. Parmar

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The chain-breaking antioxidant activities of eight coumarins [7-hydroxy-4-methylcoumarin (1), 5,7-dihydroxy-4-methylcoumarin (2), 6,7-dihydroxy-4-methylcoumarin (3), 6,7-dihydroxycoumarin (4), 7,8-dihydroxy-4-methylcoumarin (5), ethyl 2-(7,8-dihydroxy-4-methylcoumar-3-yl)-acetate (6), 7,8-diacetoxy-4-methylcoumarin (7) and ethyl 2-(7,8-diacetoxy-4-methylcoumar-3-yl)-acetate (8)] during bulk lipid autoxidation at 37 °C and 80 °C in concentrations of 0.01-1.0 mM and their radical scavenging activities at 25 °C using TLC-DPPH test have been studied and compared. It has been found that the o-dihydroxycoumarins 3-6 demonstrated excellent activity as antioxidants and radical scavengers, much better than the m-dihydroxy analogue 2 and the monohydroxycoumarin 1. The substitution at the C-3 position did not have any effect either on the chain-breaking antioxidant activity or on the radical scavenging activity of the 7,8-dihydroxy- and 7,8-diacetoxy-4-methylcoumarins 6 and 8. The comparison with DL-α-tocopherol (TOH), caffeic acid (CA) and p-coumaric acid (p-CumA) showed that antioxidant efficiency decreases in the following sequence:. TOH > CA > 3 > 4 > 6 > 5 > 2 > 1 = 7 = 8 = p-CumA.Theoretical calculations and the " Lipinski's Rule of Five" were used for explaining the structure-activity relationships and pharmacokinetic behavior. A higher TGSO oxidation stability was observed in the presence of equimolar (1:1) binary mixtures of coumarins with TOH (1 + TOH, 3 + TOH and 5 + TOH). However, the synergism (14%) was observed only for the binary mixture of 5 + TOH.

Original languageEnglish (US)
Pages (from-to)1089-1100
Number of pages12
JournalBiochimie
Volume92
Issue number9
DOIs
StatePublished - Sep 1 2010
Externally publishedYes

Fingerprint

Tocopherols
Structure-Activity Relationship
Antioxidants
Scavenging
Binary mixtures
Acetates
Coumarins
Pharmacokinetics
Substitution reactions
Lipids
Oxidation

Keywords

  • Antioxidants
  • Dihydroxy-4-methylcoumarins
  • Lipinski's rule of five
  • Structure-activity relationship
  • Synergistic effect

ASJC Scopus subject areas

  • Biochemistry

Cite this

Structure-activity relationship of dihydroxy-4-methylcoumarins as powerful antioxidants : Correlation between experimental & theoretical data and synergistic effect. / Kancheva, Vessela D.; Saso, Luciano; Boranova, Petya V.; Khan, Abdullah; Saroj, Manju K.; Pandey, Mukesh; Malhotra, Shashwat; Nechev, Jordan Z.; Sharma, Sunil K.; Prasad, Ashok K.; Georgieva, Maya B.; Joseph, Carleta; DePass, Anthony L.; Rastogi, Ramesh C.; Parmar, Virinder S.

In: Biochimie, Vol. 92, No. 9, 01.09.2010, p. 1089-1100.

Research output: Contribution to journalArticle

Kancheva, VD, Saso, L, Boranova, PV, Khan, A, Saroj, MK, Pandey, M, Malhotra, S, Nechev, JZ, Sharma, SK, Prasad, AK, Georgieva, MB, Joseph, C, DePass, AL, Rastogi, RC & Parmar, VS 2010, 'Structure-activity relationship of dihydroxy-4-methylcoumarins as powerful antioxidants: Correlation between experimental & theoretical data and synergistic effect', Biochimie, vol. 92, no. 9, pp. 1089-1100. https://doi.org/10.1016/j.biochi.2010.06.012
Kancheva, Vessela D. ; Saso, Luciano ; Boranova, Petya V. ; Khan, Abdullah ; Saroj, Manju K. ; Pandey, Mukesh ; Malhotra, Shashwat ; Nechev, Jordan Z. ; Sharma, Sunil K. ; Prasad, Ashok K. ; Georgieva, Maya B. ; Joseph, Carleta ; DePass, Anthony L. ; Rastogi, Ramesh C. ; Parmar, Virinder S. / Structure-activity relationship of dihydroxy-4-methylcoumarins as powerful antioxidants : Correlation between experimental & theoretical data and synergistic effect. In: Biochimie. 2010 ; Vol. 92, No. 9. pp. 1089-1100.
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AU - Khan, Abdullah

AU - Saroj, Manju K.

AU - Pandey, Mukesh

AU - Malhotra, Shashwat

AU - Nechev, Jordan Z.

AU - Sharma, Sunil K.

AU - Prasad, Ashok K.

AU - Georgieva, Maya B.

AU - Joseph, Carleta

AU - DePass, Anthony L.

AU - Rastogi, Ramesh C.

AU - Parmar, Virinder S.

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N2 - The chain-breaking antioxidant activities of eight coumarins [7-hydroxy-4-methylcoumarin (1), 5,7-dihydroxy-4-methylcoumarin (2), 6,7-dihydroxy-4-methylcoumarin (3), 6,7-dihydroxycoumarin (4), 7,8-dihydroxy-4-methylcoumarin (5), ethyl 2-(7,8-dihydroxy-4-methylcoumar-3-yl)-acetate (6), 7,8-diacetoxy-4-methylcoumarin (7) and ethyl 2-(7,8-diacetoxy-4-methylcoumar-3-yl)-acetate (8)] during bulk lipid autoxidation at 37 °C and 80 °C in concentrations of 0.01-1.0 mM and their radical scavenging activities at 25 °C using TLC-DPPH test have been studied and compared. It has been found that the o-dihydroxycoumarins 3-6 demonstrated excellent activity as antioxidants and radical scavengers, much better than the m-dihydroxy analogue 2 and the monohydroxycoumarin 1. The substitution at the C-3 position did not have any effect either on the chain-breaking antioxidant activity or on the radical scavenging activity of the 7,8-dihydroxy- and 7,8-diacetoxy-4-methylcoumarins 6 and 8. The comparison with DL-α-tocopherol (TOH), caffeic acid (CA) and p-coumaric acid (p-CumA) showed that antioxidant efficiency decreases in the following sequence:. TOH > CA > 3 > 4 > 6 > 5 > 2 > 1 = 7 = 8 = p-CumA.Theoretical calculations and the " Lipinski's Rule of Five" were used for explaining the structure-activity relationships and pharmacokinetic behavior. A higher TGSO oxidation stability was observed in the presence of equimolar (1:1) binary mixtures of coumarins with TOH (1 + TOH, 3 + TOH and 5 + TOH). However, the synergism (14%) was observed only for the binary mixture of 5 + TOH.

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