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Synthesis, molecular modeling, and pharmacological evaluation of new 2-substituted benzoxazole derivatives as potent anti-inflammatory agents

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Abstract

In the present work, 2-substituted benzoxazole derivatives were synthesized from 2-(benzo[d]oxazol-2-yl) aniline. All the synthesized compounds were purified and characterized by 1H NMR, 13C NMR, and mass spectroscopy. All the compounds were pharmacologically evaluated for its in vitro anti-inflammatory efficacy using membrane stabilization and proteinase inhibitory methods. In addition to this, in silico molecular docking studies were carried out to predict the binding affinity of the synthesized benzoxazole derivatives with prostaglandin H2 synthase (PGHS) protein and trypsin enzyme. The results obtained from in vitro anti-inflammatory studies showed that compound 3, 4, and 6a showed good efficacy with percentage inhibition of 74.26 ± 1.04, 80.16 ± 0.24, and 70.24 ± 0.68 for membrane stabilization activity 80.19 ± 0.05, 85.30 ± 1.04, and 75.68 ± 1.28 towards proteinase inhibitory efficacy at a concentration of 100 μg/mL which was on par to that of standards aceclofenac and etodolac. Molecular docking analysis showed that compounds 3 and 4 possess good binding affinity towards PGHS protein with a docking score of − 9.4 and − 9.3 kcal/mol respectively.

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Acknowledgements

The authors sincerely thank the management of Kalasalingam Academy of Research and Education (KARE),  Krishnankoil, Tamil Nadu, India, for their constant encouragement and support and providing all the necessary facilities for carrying out this study. The authors also thank Vellore Institute of Technology DST-VIT-FIST, SIF-VIT for carrying out NMR analysis.

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Authors and Affiliations

  1. Department of Chemistry, Kalasalingam Academy of Research and Education (Deemed to be University), Anand Nagar, Krishnankoil, Tamilnadu, 626126, India

    Gangadhara Angajala

  2. Department of Chemistry, Arignar Anna Government Arts College for women, Walajapet, Tamilnadu, 632513, India

    Radhakrishnan Subashini

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  1. Gangadhara Angajala
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Correspondence to Gangadhara Angajala.

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Angajala, G., Subashini, R. Synthesis, molecular modeling, and pharmacological evaluation of new 2-substituted benzoxazole derivatives as potent anti-inflammatory agents. Struct Chem 31, 263–273 (2020). https://doi.org/10.1007/s11224-019-01374-1

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