| Abstrakt: |
In this work, a series of phenyl‐derivatives of spirofuran‐triazolo[1,5‐a]pyrimidine (5 a–i) were evaluated for their anti‐inflammatory and analgesic activities, including SAR and molecular docking studies. The cytotoxicity of compounds was studied in RAW 264.7 murine macrophage cell line by MTT assay. Then, those with cell viability higher than 70 % were tested for their anti‐inflammatory activity at their non‐toxic doses by evaluating the nitrite level of the cell supernatants with the Griess reagent. Compounds 5 b, 5 d, 5 e, and 5 g demonstrated significant inhibition of nitrite production by 49 %, 59 %, 63 % respectively at 100 μM (p<0.05), whereas 56 % inhibition was seen with 50 μM of 5 g. According to the inhibition of PGE2, compound 5 b showed the most notable effect compared to control. All tested compounds, particularly 5 b, 5 d, 5 e and 5 f reduced the PGE2 level and showed potential analgesic activity. Seven heterocycles 5 a–g showed moderate to significant anti‐inflammatory and analgesic activities. Molecular docking predicts modest or no inhibition of 5 a–i with COX‐1. Instead, the modelling results also show that these molecules can effectively bind to the enzymes COX‐2 and mPGES‐2. However, the simulation distinguished the key role of the 2‐OH group in stabilizing the inhibitor‐target complex only in the case of binding to COX‐2. [ABSTRACT FROM AUTHOR] |
Plný text