Discovery of N-[2-(4-methylquinolin-2-yl)phenyl]acetamidine as a new potent nitric oxide synthase inhibitor against glioma progression

Gliomas are aggressive brain tumors with limited treatment options, often leading to poor patient outcomes despite surgery, radiation, and chemotherapy. Current therapies, such as temozolomide and radiation, provide only temporary control, as gliomas frequently develop resistance. Therefore, there is an urgent need for new therapeutics to improve survival and quality of life for patients. In the present study, we explore the hypothesis that the dual inhibition of both the neuronal and inducible nitric oxide synthases could represent a promising therapeutic approach, being these two enzymes often dysregulated in gliomas. To this end, the new quinoline-based compound 3 was synthetized by a simple, innovative and solvent-free procedure. The molecule was a potent dual inhibitor and demonstrated significant antitumor activity against glioma, both as a monotherapy and in combination with temozolomide.