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New anti-inflammatory thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles with antioxidant properties as potential iNOS inhibitors

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Abstract

The objective of this study was to investigate the anti-inflammatory and antioxidant activity of new thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azole derivatives as potential iNOS inhibitors. The in vivo anti-inflammatory effects of the new thiazole compounds were studied in a turpentine oil induced inflammation model. Their anti-inflammatory activity was assessed by evaluating the acute phase bone marrow response, phagocytes’ activity, NO synthesis and antioxidant capacity. The new thiazole compounds have anti-inflammatory effects by lowering bone marrow acute phase response and oxidative stress. The best anti-inflammatory and antioxidant effect was found for thiazolyl-carbonyl-thiosemicarbazides Th-1-8, thiazolyl-1,3,4-oxadiazole Th-20 and thiazolyl-1,3,4-thiadiazole Th-21. Virtual screening of thiazole derivatives against the oxygenase domain of chain A from 2Y37 revealed that all twenty-two compounds bind the active site of inducible nitric oxide synthase (iNOS). Based on the virtual screening and on the results obtained above, the activity may be due to their capacity to reduce the NO synthesis by blocking the bind of l-Arg in the active site of iNOS, the compounds binding the synthase by hydrogen bonds between the NH (2 and/or 4) of thiosemicarbazide fragment (Th-2-8) or N2/N3 from azole cycles and by the thiol function (Th-9-22).

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Acknowledgments

This work was financially supported by the National University Research Council, Romania (Project PNII-ID No. 1348/2008). This support is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Iuliu Haţieganu University of Medicine and Pharmacy, 400010, Cluj-Napoca, Romania

    Brînduşa Tiperciuc, Cristina Nastasă, Ioana Ionuţ & Ovidiu Oniga

  2. Department of Physiopathology, Faculty of Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Alina Pârvu

  3. Research and Development Department, National Institute for Research and Development for Cryogenic and Isotopic Technologies, 240050, Ramnicu Valcea, Romania

    Radu Tamaian

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  1. Brînduşa Tiperciuc
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  2. Alina Pârvu
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  4. Cristina Nastasă
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Correspondence to Brînduşa Tiperciuc.

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B. Tiperciuc, A. Pârvu and R. Tamaian contributed equally to this work.

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Tiperciuc, B., Pârvu, A., Tamaian, R. et al. New anti-inflammatory thiazolyl-carbonyl-thiosemicarbazides and thiazolyl-azoles with antioxidant properties as potential iNOS inhibitors. Arch. Pharm. Res. 36, 702–714 (2013). https://doi.org/10.1007/s12272-013-0083-9

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