posted on 2020-06-24, 18:36authored byCristina Maccallini, Fabio Arias, Marialucia Gallorini, Pasquale Amoia, Alessandra Ammazzalorso, Barbara De Filippis, Marialuigia Fantacuzzi, Letizia Giampietro, Amelia Cataldi, María Encarnación Camacho, Rosa Amoroso
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 17 emerged as the most
promising inhibitor and was evaluated on C6 rat glioma cell line,
showing antiproliferative effects and high selectivity over astrocytes.