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Synthesis and biological evaluation of new 2-(6-alkyl-pyrazin-2-yl)-1H-benz[d]imidazoles as potent anti-inflammatory and antioxidant agents

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Abstract

A novel series of 2-(6-alkyl-pyrazin-2-yl)-1H-benzo[d]imidazole analogs (3a–3j) derived from 2-(6-chloropyrazin-2-yl)-1H-benzo[d]imidazole (2) by reacting with various substituted cyclic and acyclic secondary amines in presence of Pd-PEPPSI Mes catalyst by using Buchwald–Hartwig amination in excellent yield. The structures of newly synthesized compounds were elucidated by Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance, 13C-nuclear magnetic resonance, electrospray ionisation mass spectrometry and high-resolution mass spectrometry spectral data. All the title compounds (3a–3j) were evaluated for in vitro screening against cyclooxygenase-1 and cyclooxygenase-2 by colorimetric COX (human ovine) inhibition assay and in vivo anti-inflammatory activity against cyclooxygenase-2 enzyme by means of the carrageenan-induced rat paw edema. The compound 3i was found to have potent anti-inflammatory activity than standard Ibuprofen. The compounds 3a, 3e, and 3j showed appreciable activity against cyclooxygenase-2 enzyme. However the compounds 3a, 3e, 3g, 3h, and 3j were showed maximum activity within 15 to 24 h and 3g and 3i were showed good DPPH scavenging activity. Moreover, the docking studies were also performed and the results are well agreement with the biological data, suggested that compound 3i was a potential anti-inflammatory agent for further development.

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Acknowledgements

Bhookya Shankar thanks to UGC-BSR, (RFSMS-Award No. 805/chem/2013), NEW Delhi, India for financial support in the form of senior research fellowship (SRF) and we thank IICT, Hyderabad, for providing the facilities of spectral analysis. BSK thanks to Schrödinger Glide 5.6, LLC, New York, for performing docking studies. We also thank to Jeeva life science, IDA Uppal, Hyderabad, Telangana, India for providing facilities of biological activity.

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Authors and Affiliations

  1. Department of Chemistry, University College of Science, Osmania University, Saifabad, Hyderabad, 500004, Telangana, India

    Bhookya Shankar, Pochampally Jalapathi, Anil Valeru & Angajala Kishor Kumar

  2. Molecular Modeling and Medicinal Chemistry Group, Department of Chemistry, University College of Science, Osmania University, Hyderabad, 500 007, Telangana, India

    Balabadra Saikrishna

  3. Department of Biochemistry, University College of Science, Osmania University, Hyderabad, 500007, Telangana, India

    Karunakar rao Kudle

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  1. Bhookya Shankar
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  2. Pochampally Jalapathi
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  5. Balabadra Saikrishna
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Correspondence to Pochampally Jalapathi.

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Shankar, B., Jalapathi, P., Valeru, A. et al. Synthesis and biological evaluation of new 2-(6-alkyl-pyrazin-2-yl)-1H-benz[d]imidazoles as potent anti-inflammatory and antioxidant agents. Med Chem Res 26, 1835–1846 (2017). https://doi.org/10.1007/s00044-017-1897-7

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  • DOI: https://doi.org/10.1007/s00044-017-1897-7

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