Parallel synthesis, evaluation, and preliminary structure-activity relationship of 2,5-diamino-1,4-benzoquinones as a novel class of bivalent anti-prion compound.
A library of 11 entries, featuring a 2,5-diamino-1,4-benzoquinones nucleus as spacer connecting two aromatic prion recognition motifs, was designed and evaluated against prion infection. Notably, 6-chloro-1,2,3,4-tetrahydroacridine 10 showed an EC(50) of 0.17 μM, which was lower than that displayed by reference compound BiCappa. More importantly, 10 possessed the capability to contrast prion fibril formation and oxidative stress, together with a low cytotoxicity. This study further corroborates the bivalent strategy as a viable approach to the rational design of anti-prion chemical probes.
Statistical and Biological Physics Sector, Neurobiology Sector, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Via Bonomea 265, 34136 Trieste, Italy.
Salvatore
S
Bongarzone
Hoang Ngoc Ai
HN
Tran
Andrea
A
Cavalli
Marinella
M
Roberti
Paolo
P
Carloni
Giuseppe
G
Legname
Maria Laura
ML
Bolognesi
D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D016227:Benzoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D018620:PrPSc Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
C554515:6-chloro-1,2,3,4-tetrahydroacridine; D000166:Acridines; D000588:Amines; D016227:Benzoquinones; D018620:PrPSc Proteins