Pharmaceutical Chemistry Journal, vol.56, no.6, pp.769-776, 2022 (SCI-Expanded)
© 2022, Springer Science+Business Media, LLC, part of Springer Nature.Biological activity of the Biginelli type heterocycles is extremely broad and provides a suitable platform for the discovery of potent small drug-like molecules. Such activity of 3,4-dihydropyrimidin-2(1H)-one (DHPM) derivatives is widely known, whereas their oxygen-bridged analogs, benzoxadiazocines, are presented quite rarely in the literature. In this study, a series of new methano[1,2,4]triazolo[1,5-c][1,3,5]benzoxadiazocine derivatives (3a-3j) were evaluated in vitro for their activities and molecular docking features. According to the molecular docking study, COX-2 and PGE2S appeared as likely targets responsible for the reduced PGE2 levels caused by the title compounds. The cytotoxicity of compounds 3a-3g, 3j was evaluated on RAW 264.7 murine macrophage cell line by MTT assay after treatment for 24 h with various doses (25, 50, 100 μM) of these compounds. Then, compounds admitting cell viability higher than 70% were tested for their anti-inflammatory activity at non-toxic doses by evaluating the nitrite level of cell supernatants with the Griess reagent. Compounds 3c and 3f demonstrated significant inhibition of nitrite production (by 29 and 25%, respectively) at 100 μM (p < 0.05). These compounds significantly inhibited PGE2 production, thus suggesting analgesic activity.