Recent Advances on Nitrones Design for Stroke Treatment

The recent advances of tetramethylpyrazine nitrones and quinolylnitrones for the treatment of stroke have been reviewed and compared with other agents, showing promising therapeutic applications. As a result of a functional transformation of natural product ligustrazine, (Z)-N-tert-butyl-1-(3,5,6-trimethylpyrazin-2-yl)methanimine oxide (6) is a multitarget small nitrone showing potent thrombolytic activity and free radicals scavenging power, in addition to nontoxicity and blood-brain barrier permeability. Similarly, antioxidant (Z)-N-tert-butyl-1-(2-chloro-6-methoxyquinolin-3-yl)methanimine oxide (17) is a novel agent for cerebral ischemia therapy as it is able to scavenge different types of free radical species, showing strong neuroprotection and reduced infarct size.J.M.-C. thanks MINECO (Government of Spain, GrantSAF2015-65586-R), UCJC (Grants UCJC 2020-03 and UCJC2020-33), and ISCIII (Grant RD06/0026/1002) for support.J.M.-C. thanks Dr. Alcàzar (Department of Investigation,IRYCIS, Hospital Ramón y Cajal, Madrid, Spain), Prof. Oset-Gasque (Department of Biochemistry and Molecular Biology II,School of Pharmacy, UCM, Madrid, Spain), and Prof.Piotrowska (Faculty of Pharmacy, Medical University of Lodz,Poland) for continued collaboration. J.M.-C. also thanks theRENEVAS staff, in particular Pepe Castillo, Nacho Lizasoaìn,Marìa A. Moro, Antonio Dàvalos, and Joan Montaner, forstimulating and fruitful discussions. Figures 5−7 and Table 1 area reproduction of Figures 4, 7, 11, and Table 1, respectively, fromref66; Figures 9 and 10 are a reproduction of Figures 1 and 2,respectively, from ref65; Figure 12 is a reproduction of Figure 5from ref77, and for these reasons I thank the author