These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Design and Synthesis of Novel 1,3,4-Oxadiazole and 1,2,4-Triazole Derivatives as Cyclooxygenase-2 Inhibitors with Anti-inflammatory and Antioxidant activity in LPS-stimulated RAW264.7 Macrophages.
    Author: Hamoud MMS, Osman NA, Rezq S, A A Abd El-Wahab H, E A Hassan A, Abdel-Fattah HA, Romero DG, Ghanim AM.
    Journal: Bioorg Chem; 2022 Jul; 124():105808. PubMed ID: 35447409.
    Abstract:
    In an attempt to obtain new candidates with potential anti-inflammatory activity, two series of 1,3,4-oxadiazole based derivatives (8a-g) and 1,2,4-triazole based derivatives (10a,b and 11a-g) were synthesized and evaluated for their COX-1/COX-2 inhibitory activity. In vitro assays showed potent COX-2 inhibitory activity and selectivity of the novel designed compounds (IC50 = 0.04 - 0.16 μM, SI = 60.71 - 337.5) compared to celecoxib (IC50 = 0.045 μM, SI = 326.67). The anti-inflammatory and antioxidant activity of the synthesized compounds was investigated via testing their ability to inhibit pro-inflammatory [tumour necrosis factor (TNF-α) and interleukin-6 (IL-6)] and oxidative stress [nitric oxide (NO) and reactive oxygen species (ROS)] markers production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. Most of the novel compounds exhibited potent anti-inflammatory and antioxidant activity. In particular, the novel compounds showed excellent IL-6 inhibitory activity (IC50 = 0.96 - 11.14 μM) when compared to celecoxib (IC50 = 13.04 μM) and diclofenac sodium (IC50 = 22.97 μM). Moreover, the most potent and selective COX-2 inhibitor 11c (IC50 = 0.04 μM, SI = 337.5) displayed significantly higher activity against NO and ROS production compared to celecoxib (IC50 = 2.60 and 3.01 μM vs. 16.47 and 14.30 μM, respectively). Molecular modelling studies of the novel designed molecules into COX-2 active sites analysed their binding affinity. In-silico simulation studies indicated their acceptable physicochemical properties and pharmacokinetic profiles. This study suggests that the novel synthesized COX-2 inhibitors exert potent anti-inflammatory and antioxidant activity, highlighting their potential as promising therapeutic agents for the treatment of inflammation and oxidative stress-related diseases.
    [Abstract] [Full Text] [Related] [New Search]