Benzothiazole Schiff-bases as potential imaging agents for β-amyloid plaques in Alzheimer’s disease
- 464 Downloads
A series of benzothiazole Schiff-bases as potential diagnostic imaging agents targeting β-amyloid (Aβ) plaques in Alzheimer’s disease (AD) were synthesized and evaluated. When in vitro binding studies using AD homogenate with [125I] 6-iodo-2-(4′-dimethyl- amino)-phenyl-imidazo[1,2-α]pyridine ([125I]IMPY) as the reference ligand were carried out with the derivatives, the compounds showed high to low binding affinities for AD homogenate at the K i values ranged from 4.38 to 514.65 nM, depending on the substitution on the phenyl ring. Fluorescent staining in vitro showed that one compound with a N,N-dimethylamino group intensely stained Aβ plaques within brain sections of postmortem AD patients. The results strongly suggest that these derivatives are worthy of further study and may be a useful amyloid imaging agents for early detection of amyloid plaques in the brain of AD.
KeywordsAlzheimer’s disease Amyloid plaques Benzothiazole Schiff-bases Binding affinity
We are grateful to the Key Laboratory of Brain Function and Disease, Chinese Academy of Sciences for financial support.
- Klunk WE, Engler H, Nordberg A, Wang Y, Blomqvist G, Holt DP, Bergstrom M, Savitcheva I, Huang GF, Estrada S, Ausen B, Debnath ML, Barletta J, Price JC, Sandell J, Lopresti BJ, Wall A, Koivisto P, Antoni G, Mathis CA, Langstrom B (2004) Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 55:306–319PubMedCrossRefGoogle Scholar
- Kudo Y, Okamura N, Furumoto S, Tashiro M, Furukawa K, Maruyama M, Itoh M, Iwata R, Yanai K, Arai H (2007) 2-(2-[2-Dimethylaminothiazol-5-yl]ethenyl)-6-(2-[fluoro]ethoxy)benzoxazole: a novel PET agent for in vivo detection of dense amyloid plaques in Alzheimer’s disease patients. J Nucl Med 48:553–561PubMedCrossRefGoogle Scholar
- Lee CW, Zhuang ZP, Kung MP, Plössl K, Skovronsky D, Gur T, Hou C, Trojanowski JQ, Lee VM, Kung HF (2001) Isomerization of (Z, Z) to (E, E)1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)- styrylbenzene in strong base: probes for amyloid plaques in the brain. J Med Chem 44:2270–2275PubMedCrossRefGoogle Scholar
- Nelissen N, Van Laere K, Thurfjell L, Owenius R, Vandenbulck M, Koole M, Bormans G, Brooks DJ, Vandenberghe R (2009) Phase 1 study of the Pittsburgh Compound B derivative 18F-flutemetamol in healthy volunteers and patients with probable Alzheimer disease. J Nucl Med 50:1251–1259PubMedCrossRefGoogle Scholar
- Rowe CC, Ackerman U, Browne W, Mulligan R, Pike KL, O’Keefe G, Tochon-Danguy H, Chan G, Berlangieri SU, Jones G, Dickinson-Rowe KL, Kung HP, Zhang W, Kung MP, Skovronsky D, Dyrks T, Holl G, Krause S, Friebe M, Lehman L, Lindemann S, Dinkelborg LM, Masters CL, Villemagne VL (2008) Imaging of amyloid beta in Alzheimer’s disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism. Lancet Neurol 7:129–135PubMedCrossRefGoogle Scholar
- Shoghi-Jadid K, Small GW, Agdeppa ED, Kepe V, Ercoli LM, Siddarth P, Read S, Satyamurthy N, Petric A, Huang SC, Barrio JR (2002) Localization of neurofibrillary tangles and beta-amyloid plaques in the brains of living patients with Alzheimer disease. Am J Geriatr Psychiatry 10:24–35PubMedGoogle Scholar
- Wong DF, Rosenberg PB, Zhou Y, Kumar A, Raymont V, Ravert HT, Dannals RF, Nandi A, Brasic JR, Hilton J, Lyketsos C, Kung HF, Joshi AD, Skovronsky DM, Pontecorvo MJ (2010) In vivo imaging of amyloid deposition in Alzheimer disease using the radioligand 18F-AV-45 (florbetapir F 18). J Nucl Med 51:913–920PubMedCrossRefGoogle Scholar