Structure-activity relationships of memoquin: Influence of the chain chirality in the multi-target mechanism of action.
The present article expands on the study of structure-activity relationships of the novel class of quinone-bearing polyamines, as multi-target-directed ligands against Alzheimer's disease. Namely, the effect of inserting a methyl substituent at the alpha position of the terminal benzyl amine moieties of lead candidate 1 (memoquin) was evaluated at the multiple targets involved in the multifunctional mechanism of action. The RR stereoisomer 2 resulted more effective than 1 in reverting two important effects mediated by acetylcholinesterase (AChE), that is, acetylcholine hydrolysis and AChE-induced amyloid-beta aggregation.
Bolognesi
Maria Laura
ML
Department of Pharmaceutical Sciences, Alma Mater Studiorum-Bologna University, Via Belmeloro 6, I-40126 Bologna, Italy. marialaura.bolognesi@unibo.it
Bartolini
Manuela
M
Rosini
Michela
M
Andrisano
Vincenza
V
Melchiorre
Carlo
C
D000110:Acetylcholinesterase / Q000737:chemistry; D000473:Alkanes / Q000138:chemical synthesis* / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy; D000588:Amines / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D011073:Polyamines / Q000737:chemistry; D011809:Quinones / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000473:Alkanes; D000588:Amines; D016229:Amyloid beta-Peptides; D005021:Ethylamines; D011073:Polyamines; D011809:Quinones; C521476:memoquin; D000110:Acetylcholinesterase