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Design, synthesis and molecular docking of some new 1,2,4-triazolobenzimidazol-3-yl acetohydrazide derivatives with anti-inflammatory-analgesic activities

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Abstract

The present work describes the synthesis and evaluation of some new acetohydrazones, 1,3,4-oxadiazoles and 1,2,4-triazoles of 1,2,4-triazolo[1,5-a]benzimidazole as anti-inflamm atory-analgesic agents. Structure elucidation of these compounds was confirmed by IR, 1H NMR, and mass spectrometry along with elemental microanalyses. Most compounds exhibited significant anti-inflammatory activity in comparison to indomethacin. Further, some compounds were tested for their analgesic effects where two compounds showed results comparable to indomethacin at 4 h interval. The most active anti-inflammatory and analgesic compounds (4c and 11a) were examined on gastric mucosa and didn’t show any gastric ulcerogenic effect compared with the reference indomethacin. Moreover, LD50 of compounds (4c and 11a) were determined in mice; they were found non toxic up to 240 and 300 mg/kg (i.p.). Also, docking simulation of some compounds into COX active sites was studied.

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Acknowledgments

The authors are greatly indepted to Dr. Safwat A. Mankora, Professor Dept. Pharmacology, Faculty of Medicine, Assiut University, Egypt, for his kind supervision of performing the anti-inflammatory-analgesic activities. The authors, also, extend their gratitude to Dr. Mohammed K. Abdel-Hamid, Lecturer of Medicinal Chemistry, Medicinal Chemistry Dept., Faculty of Pharmacy, Assiut University, Egypt, for revising and making the required alterations to the molecular modeling discussion. Also, we are grateful to the Department of medicinal Chemistry for allowing its facility to performing the docking and alignment studies.

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  1. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, 71526, Egypt

    Anber F. Mohammed, Samia G. Abdel-Moty, Mostafa A. Hussein & Abdel-Alim M. Abdel-Alim

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  1. Anber F. Mohammed
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  2. Samia G. Abdel-Moty
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  3. Mostafa A. Hussein
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  4. Abdel-Alim M. Abdel-Alim
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Correspondence to Samia G. Abdel-Moty.

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Mohammed, A.F., Abdel-Moty, S.G., Hussein, M.A. et al. Design, synthesis and molecular docking of some new 1,2,4-triazolobenzimidazol-3-yl acetohydrazide derivatives with anti-inflammatory-analgesic activities. Arch. Pharm. Res. 36, 1465–1479 (2013). https://doi.org/10.1007/s12272-013-0153-z

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