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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

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Pharmaceutical Chemistry Journal Aims and scope

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.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey

    İnci Selin Doğan

  2. Science-Technology Research and Application Center, Artvin Coruh University, Artvin, Turkey

    Mustafa Kemal Gümüş

  3. Department of Organic and Bioorganic Chemistry, SSI “Institute for Single Crystals” of National Academy of Sciences of Ukraine, Kharkiv, Ukraine

    Nikolay Yu. Gorobets & Valentyn A. Chebanov

  4. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Acybadem Mehmet Ali Aydýnlar University, Istanbul, Turkey

    Rengin Reis

  5. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Yeditepe University, Istanbul, Turkey

    Rengin Reis & Hande Sipahi

  6. Drug, Cosmetic and Medical Device Research-Development and Analysis Laboratory, Faculty of Pharmacy, Yeditepe University, Istanbul, Turkey

    Duygu Orak

  7. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

    Suat Sari

  8. Department of Applied Chemistry, V. N. Karazin Kharkiv National University, Kharkiv, Ukraine

    Valentyn A. Chebanov

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  1. İnci Selin Doğan
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Correspondence to Mustafa Kemal Gümüş.

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Doğan, İ.S., Gümüş, M.K., Gorobets, N.Y. et al. 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. Pharm Chem J 56, 769–776 (2022). https://doi.org/10.1007/s11094-022-02708-w

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