Doğan, İnci SelinGümüş, Mustafa KemalGorobets, Nikolay YuReis, RenginOrak, DuyguSipahi, HandeSarı, SuatChebanov, Valentyn A.2022-09-302022-09-302022Doğan, İ. S., Gümüş, M. K., Gorobets, N. Y., Reis, R., Orak, D., Sipahi, H., ... & Chebanov, V. A. (2022). In Vitro Cytotoxicity of Methano [1, 2, 4] Triazolo-[1, 5-C][1, 3, 5] Benzoxadiazocine Derivatives and Their Effects on Nitrite and Prostaglandin E2 (PGE2) Levels. Pharmaceutical Chemistry Journal.https://hdl.handle.net/11494/4255Biological 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 PGE(2)S appeared as likely targets responsible for the reduced PGE(2) 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 mu M) 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 mu M (p < 0.05). These compounds significantly inhibited PGE(2) production, thus suggesting analgesic activity.eninfo:eu-repo/semantics/closedAccessanti-inflammatory activityanalgesicBiginelli reactionin vitro cytotoxicitymolecular dockingnitrite levelPGE(2)Article10.1007/s11094-022-02708-wQ4Q4