Diversified Thiazole Substituted Coumarins and Chromones as Non- Cytotoxic ROS and NO Inhibitors

Author(s): Uzma Salar, Khalid Mohammed Khan*, Almas Jabeen, Shafquat Hussain, Aisha Faheem, Farwa Naqvi, Shahnaz Perveen.

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 5 , 2020

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Graphical Abstract:


Background: Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, aspirin, indomethacin, flufenamic acid and phenylbutazone are used to treat most of the inflammatory disorders. These NSAIDs are also associated with serious side effects including gastric ulceration, nephrotoxicity, and bleeding, mainly due to acidic nature. Hence, there is a need to identify highly potent and safer treatment for inflammatory disorders.

Methods: Herein, synthetic hydrazinyl thiazole substituted coumarins and chromones 1-48 were evaluated for ROS inhibitory activity. ROS were generated from zymosan activated whole blood phagocytes.

Results: Among all tested compounds, compounds 1 (IC50 = 38.3 ± 7.1 μM), 2 (IC50 = 5.7 ± 0.2 μM), 5 (IC50 = 28.3 ± 3.5 μM), 23 (IC50 = 12.5 ± 3.1 μM), 27 (IC50 = 32.8 ± 1.1 μM), 39 (IC50 = 20.2 ± 1.6 μM), and 42 (IC50 = 43.2 ± 3.8 μM) showed potent ROS inhibition as compared to standard ibuprofen (IC50 = 54.3 ± 1.9 μM). Whereas, compounds 3 (IC50 = 134.7 ± 1.0 μM), 16 (IC50 = 75.4 ± 7.2 μM), 24 (IC50 = 102.4 ± 1.0 μM), and 31 (IC50 = 86.6 ± 1.5 μM) were found to be moderately active. Compounds 1, 2, 5, 23, 27, 39, and 42, having potent ROS inhibitory activity were also screened for their nitric oxide (NO) inhibition. Cytotoxicity was also checked for all active compounds on NIH-3T3 cell line. Cyclohexamide (IC50 = 0.13 ± 0.02 μM) was used as standard.

Conclusion: Identified active compounds from these libraries may serve as lead candidates for future research in order to obtain a more potent, and safer anti-inflammatory agent.

Keywords: Coumarin, chromone, thiazole, ROS, nitric oxide, cytotoxicity, antiinflammatory, ibuprofen, structure-activity relationship.

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Year: 2020
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DOI: 10.2174/1570180816666190611155218
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