Pyrimidine Derivatives as Selective COX-2 Inhibitors with Anti-Inflammatory and Antioxidant Properties.

Autor: Tylińska B; Department of Organic Chemistry, Wroclaw Medical University, Borowska 211A, 50-556 Wroclaw, Poland., Janicka-Kłos A; Department of Basic Chemical Sciences, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, Poland., Gębarowski T; Department of Biostructure and Animal Physiology, The Wroclaw University of Environmental and Life Sciences, Kożuchowska 1/3, 51-631 Wroclaw, Poland., Nowotarska P; Department of Biostructure and Animal Physiology, The Wroclaw University of Environmental and Life Sciences, Kożuchowska 1/3, 51-631 Wroclaw, Poland., Plińska S; Department of Basic Chemical Sciences, Wroclaw Medical University, Borowska 211a, 50-556 Wrocław, Poland., Wiatrak B; Department of Pharmacology, Wroclaw Medical University, Mikulicza-Radeckiego 2, 50-345 Wrocław, Poland.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Oct 13; Vol. 25 (20). Date of Electronic Publication: 2024 Oct 13.
DOI: 10.3390/ijms252011011
Abstrakt: Pyrimidine derivatives exhibit a wide range of biological activities, including anti-inflammatory properties. The aim of this study was to investigate the effects of tested pyrimidine derivatives on the activity of cyclooxygenase isoenzymes (COX-1 and COX-2), antioxidant properties, and their ability to inhibit the growth of inflammatory cells. In vitro tests were conducted to assess the ability of pyrimidine derivatives L1-L4 to inhibit COX-1 and COX-2 activity using the TMPD oxidation assay (N,N,N',N'-tetramethyl-p-phenylenediamine). The compounds' ability to inhibit the growth of lipopolysaccharide (LPS)-stimulated THP-1 (human leukemia monocytic) monocyte cells and their impact on reactive oxygen species (ROS) levels in an inflammatory model were also evaluated. The binding properties of human serum albumin (HSA) were assessed using UV-Vis spectroscopy, circular dichroism (CD), and isothermal titration calorimetry (ITC). Among the tested pyrimidine derivatives, L1 and L2 showed high selectivity towards COX-2, outperforming piroxicam and achieving results comparable to meloxicam. In the sulforhodamine B (SRB) assay, L1 and L2 demonstrated dose-dependent inhibition of LPS-stimulated THP-1 cell growth. Additionally, ROS assays indicated that these compounds reduced free radical levels, confirming their antioxidant properties. Binding studies with albumin revealed that L1 and L2 formed stable complexes with HSA. These results suggest that these compounds could serve as a basis for further research into anti-inflammatory and anticancer drugs with reduced toxicity.
Competing Interests: The authors declare no conflicts of interest.
Databáze: MEDLINE
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