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Journal of Chemical Sciences

, Volume 129, Issue 5, pp 623–636 | Cite as

Synthesis of novel bis-allyloxy and hydroxypropoxy derivatives of 4, 5-diaryl thiophene-2-carboxylic acid and their biological evaluation

  • T Shanmuganathan
  • M Venugopal
  • K Parthasarathy
  • N Dhatchanamoorthy
  • Y Arun
  • A A M Prince
Regular Article
  • 101 Downloads

Abstract

In our earlier studies, we have shown that the introduction of amino moieties at carboxylic acid of 4,5-diarylthiophene-2-carboxylic acid significantly improved the anti-inflammatory activity of the compound against the standard drug diclofenac sodium. In the present study, we have synthesized new derivatives of 4,5-diarylthiophene-2-carboxylic acid by modifying the hydroxyl group of the phenyl ring and carboxylic acid group of the thiophene ring. A series of novel 4,5-diarylthiophene-2-carboxylic acid derivatives containing bis-allyloxy and hydroxypropoxy with methyl or ethyl ester moieties were synthesized, characterized and subsequently evaluated for anti-inflammatory and antioxidant property. Among the novel compounds, the inhibition of bovine serum albumin denaturation assay revealed that the compound 4,5-bis(4-(3-hydroxypropoxy)phenyl)thiophene-2-carboxylic acid (15) and ethyl ester (13) having anti-inflammatory activity better than the standard drug diclofenac sodium. The antioxidant screening showing 4,5-bis(4-(allyloxy)phenyl)thiophene-2-carboxylic acid (10), 4,5-bis(4-(3-hydroxypropoxy)phenyl)thiophene-2-carboxylic acid methyl ester (11) and 4,5-bis(4-(3-hydroxypropoxy)phenyl)thiophene-2-carboxylic acid ethyl ester (13) exhibited a slightly moderate antioxidant activity than standard ascorbic acid. Molecular docking analysis was performed for the synthesized compounds with the cyclooxygenase-2 (COX-2) receptor (PDB 1D: 1PXX). Docking studies revealed that all the synthesised compounds exhibit greater binding affinity than the standard drug. Particularly, the compound ethyl 4,5-bis(4-(allyloxy)phenyl)thiophene-2-carboxylate (8) and allyl 4,5-bis(4-(allyloxy)phenyl)thiophene-2-carboxylate (9) having high free energy binding of −10.40 and −10.48 Kcal/mol, respectively.

Graphical Abstract.

Synopsis: A new series of bis-allyloxy and hydroxypropoxy substituted 4,5-diarylthiophene-2-carboxylic acid derivatives were synthesized, characterized, evaluated their in vitro anti-inflammatory and anti-oxidant activity, and performed molecular docking study.

Keywords

Bis-allyloxy derivatives hydroxypropoxy derivatives 4,5-diarylthiophene-2-carboxylic acid anti-inflammatory antioxidant molecular docking 

Notes

Acknowledgements

The authors are thankful to the management of Orchid Pharma Limited, Chennai 600 119, India and Ramakrishna Mission Vivekananda College, Chennai 600 004, India for providing the required facilities.

Supplementary material

12039_2017_1274_MOESM1_ESM.docx (17.9 mb)
Supplementary material 1 (docx 18315 KB)

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Copyright information

© Indian Academy of Sciences 2017

Authors and Affiliations

  • T Shanmuganathan
    • 1
    • 2
  • M Venugopal
    • 3
  • K Parthasarathy
    • 4
  • N Dhatchanamoorthy
    • 1
  • Y Arun
    • 5
  • A A M Prince
    • 2
  1. 1.Orchid Pharma Ltd, R&D CentreChennaiIndia
  2. 2.Department of chemistryRamakrishna Mission Vivekananda CollegeChennaiIndia
  3. 3.Ven Biotech Private LimitedChennaiIndia
  4. 4.Department of Chemistry, Siddha Central Research InstituteCentral Council for Research in SiddhaChennaiIndia
  5. 5.Organic Chemistry DivisionCentral Leather Research Institute (CSIR)ChennaiIndia

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