Current healthcare has significantly increased the average life expectancy, leading to a consequently greater incidence of age-related diseases, such as Alzheimer's disease. Following a multitarget approach, in this paper a series of polycyclic maleimide-based derivatives were designed and synthesized aimed at simultaneously modulate neuronal calcium channels and glycogen synthase kinase 3-beta (GSK-3β), validated targets to combat Alzheimer’ disease. Different structural modifications were performed on the polycyclic scaffold in order to investigate the structure-activity relationships and compound 10 emerged as a promising non-toxic lead compound, endowed with calcium modulating brain-addressed properties and significant GSK-3β inhibitory activity. Moreover, the easily affordable polycyclic core appears as a new appealing privileged structure in medicinal chemistry.
Polycyclic maleimide-based derivatives as first dual modulators of neuronal calcium channels and GSK-3β for Alzheimer's disease treatment / Bisi, Alessandra; Arribas, Raquel L.; Micucci, Matteo; Budriesi, Roberta; Feoli, Alessandra; Castellano, Sabrina; Belluti, Federica; Gobbi, Silvia; de los Rios, Cristobal; Rampa, Angela*. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 163:(2019), pp. 394-402. [10.1016/j.ejmech.2018.12.003]
Polycyclic maleimide-based derivatives as first dual modulators of neuronal calcium channels and GSK-3β for Alzheimer's disease treatment
Bisi, Alessandra
;Micucci, Matteo;Budriesi, Roberta;Belluti, Federica;Gobbi, Silvia;Rampa, Angela
2019
Abstract
Current healthcare has significantly increased the average life expectancy, leading to a consequently greater incidence of age-related diseases, such as Alzheimer's disease. Following a multitarget approach, in this paper a series of polycyclic maleimide-based derivatives were designed and synthesized aimed at simultaneously modulate neuronal calcium channels and glycogen synthase kinase 3-beta (GSK-3β), validated targets to combat Alzheimer’ disease. Different structural modifications were performed on the polycyclic scaffold in order to investigate the structure-activity relationships and compound 10 emerged as a promising non-toxic lead compound, endowed with calcium modulating brain-addressed properties and significant GSK-3β inhibitory activity. Moreover, the easily affordable polycyclic core appears as a new appealing privileged structure in medicinal chemistry.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
