Maccallini Cristina, Arias Fabio, Gallorini Marialucia, Amoia Pasquale, Ammazzalorso Alessandra, De Filippis Barbara, Fantacuzzi Marialuigia, Giampietro Letizia, Cataldi Amelia, Camacho María Encarnación, Amoroso Rosa
Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, Via dei Vestini, 31-66100 Chieti, Italy.
Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
ACS Med Chem Lett. 2020 Jun 19;11(7):1470-1475. doi: 10.1021/acsmedchemlett.0c00285. eCollection 2020 Jul 9.
Nitric oxide is an important inflammation mediator with a recognized role in the development of different cancers. Gliomas are primary tumors of the central nervous system with poor prognosis, and the expression of the inducible nitric oxide synthase correlates with the degree of malignancy, changes in vascular reactivity, and neo-angiogenesis. Therefore, targeting the nitric oxide biosynthesis appears as a potential strategy to impair glioma progression. In the present work a set of aryl and amido-aryl acetamidine derivatives were synthesized to obtain new potent and selective inducible nitric oxide synthase inhibitors with improved physicochemical parameters with respect to the previously published molecules. Compound emerged as the most promising inhibitor and was evaluated on C6 rat glioma cell line, showing antiproliferative effects and high selectivity over astrocytes.
一氧化氮是一种重要的炎症介质，在不同癌症的发展中具有公认的作用。胶质瘤是中枢神经系统的原发性肿瘤，预后较差，诱导型一氧化氮合酶的表达与恶性程度、血管反应性变化和新生血管形成相关。因此，靶向一氧化氮生物合成似乎是一种潜在的抑制胶质瘤进展的策略。在本研究中，合成了一组芳基和酰胺基芳基脒衍生物，以获得相对于先前发表的分子具有改善的物理化学参数的新型强效和选择性诱导型一氧化氮合酶抑制剂。化合物成为最有前景的抑制剂，并在C6大鼠胶质瘤细胞系上进行了评估，显示出抗增殖作用以及对星形胶质细胞的高选择性。
