Synthesis and SAR Study of Antioxidant Potential of Polyhydroxy Coumarin Derivatives

Badri Parshad,Arul J Duraisamy

doi:10.4172/2161-0444.1000391

Badri Parshad, Arul J Duraisamy

Open Access

https://doi.org/10.4172/2161-0444.1000391

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Journal: Medicinal chemistry	Publication Date: Jan 1, 2016
Citations: 25	License type: cc-by

Affiliation: University of Delhi

Abstract

A series of polyhydroxycoumarin derivatives, that are analogs of naturally occurring compounds, have been synthesized and their antioxidant activity (AOA) examined using DPPH, ABTS, and in vitro lipid peroxidation inhibition assays. The SAR for differently substituted polyhydroxycoumarins is reported by evaluating the positional effect of hydroxyl groups and the effect of incorporation of the lipophilic group on antioxidant activity. Many of the compounds synthesized have 4-5 fold higher AOA than ‘Trolox’ taken as standard. In DPPH and ABTS assays, the trihydroxycoumarins were observed to have a potent antioxidant activity. It has been observed that alkylation at C-3/C-4 position as well as the incorporation of pyran ring on coumarin skeleton led to the reduction in AOA in the above two assays. However, in lipid peroxidation inhibition assay an enhancement in AOA was observed for such modifications. The rationale for the observance of variation in AOA in different assays is also studied.

Highlights

Antioxidant enzymes are known to control oxidative stress by preventing the Reactive Oxygen/Nitrogen Species (ROS/RNS) induced damage to biomembranes, nucleic acids, proteins, etc
A poor yield of the product was obtained by using isoprene in place of 2-methyl-3-buten-2-ol as a reactant. 5,6,7-Trihydroxy-4-methylcoumarin (25) was synthesized by demethylation of 5,6,7-trimethoxy-4-methylcoumarin (24) in HBr-acetic acid
The enhancement in AOA with increase in alkyl chain length in lipid peroxidation assay (LPO) assay has been previously observed by our group [12] and Takahashi et al [31]. These results suggests that the incorporation of the hydrophobic group on the pyranocoumarin enhances the interaction of resulting compound with lipids and improves the antioxidant activity

Summary

Introduction

Antioxidant enzymes are known to control oxidative stress by preventing the Reactive Oxygen/Nitrogen Species (ROS/RNS) induced damage to biomembranes, nucleic acids, proteins, etc. The method of evaluation of antioxidant capacity of a molecule involve radical scavenging or radical formation inhibition and follow either homolytic hydrogen atom transfer (HAT) or single electron transfer (SET). In HAT, a hydrogen atom from the antioxidant (ArOH) is captured by the free radical and antioxidant itself becomes a radical. Polyphenolics follow such a mechanism due to their ability of phenoxide ion delocalization. SET on the other hand led to the generation of a radical cation due to the transfer of an electron from the antioxidant to the free radical. The stability of radical cation is an important criterion for the evaluation of antioxidant potential so that it itself does not react further with the substrate molecules. An antioxidant may follow either HAT and SET mechanisms simultaneously or one mechanism can outweigh the other and this is dictated by the chosen analytical method and conditions [3,4]

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Conclusion