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Novel approach of multi-targeted thiazoles and thiazolidenes toward anti-inflammatory and anticancer therapy—dual inhibition of COX-2 and 5-LOX enzymes

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Abstract

It is well established that cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) play a vital role in the initiation and progression of inflammatory reactions. Hence, thiazole and thiazolidene-based pharmacophore molecules were synthesized to obtain dual COX-2 and 5-LOX inhibitory activity. The synthesis of target compounds has been achieved by a novel green strategy. In vitro COX-1, COX-2, and 5-LOX evaluation of these molecules have shown the potential for an improved anti-inflammatory profile. Most promising compound among the series (2-(diphenylamino)-4-(4-nitrophenyl)thiazol-5-yl)(naphthalen-1-yl)methanone 7h (IC50 = 0.07 ± 0.02 μM) showed equivalent COX-2 inhibitory potency as that of positive control etoricoxib (IC50 = 0.07 ± 0.01 μM) and an enhanced selectivity index of 115.14. Compound 7h exhibited 5-LOX IC50 of 0.29 ± 0.09 μM and reference drug zileuton showed IC50 of 0.15 ± 0.05 μM. In vivo studies of 7h including carrageenan-induced paw edema assay (63% inhibition of paw edema), antiulcer studies, biochemical assays, qRT-PCR analysis, and anticancer studies indicated that the present study has identified a good lead compound for the development of a potential anti-inflammatory drug having improved gastric safety profile.

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Acknowledgements

The authors greatly acknowledge VIT, Vellore for providing “VIT Seed Grant” for research. Jaismy Jacob P recognizes CSIR, Govt. of India, for the financial support through Senior Research Fellowship for research.

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  1. Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore, Tamil Nadu, India

    Jaismy Jacob P & Manju S L

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P, J.J., S L, M. Novel approach of multi-targeted thiazoles and thiazolidenes toward anti-inflammatory and anticancer therapy—dual inhibition of COX-2 and 5-LOX enzymes. Med Chem Res 30, 236–257 (2021). https://doi.org/10.1007/s00044-020-02655-9

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