Gallorini Marialucia, Amoroso Rosa, Cataldi Amelia, Maccallini Cristina
Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy.
Mol Divers. 2025 Aug 5. doi: 10.1007/s11030-025-11309-0.
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.
胶质瘤是侵袭性脑肿瘤，治疗选择有限，尽管进行了手术、放疗和化疗，患者预后往往仍很差。目前的治疗方法，如替莫唑胺和放疗，只能提供暂时的控制，因为胶质瘤经常产生耐药性。因此，迫切需要新的治疗方法来提高患者的生存率和生活质量。在本研究中，我们探讨了一种假说，即同时抑制神经元型和诱导型一氧化氮合酶可能是一种有前景的治疗方法，因为这两种酶在胶质瘤中经常失调。为此，通过一种简单、创新且无溶剂的方法合成了新型喹啉基化合物3。该分子是一种有效的双重抑制剂，无论是作为单一疗法还是与替莫唑胺联合使用，都对胶质瘤表现出显著的抗肿瘤活性。
