Assessing the ability of newly synthesized compounds to detect amyloid fibril formation

Assessing the ability of newly synthesized compounds to detect amyloid fibril formation
Seyyed Abolghasem Ghadami,^1,* Hadi Adibi,²
1. Department of Biotechnology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
2. Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
Introduction: Neurodegenerative diseases are characterized by the presence of amyloid deposition. Many probes have been choice to attempt the detection of the amyloid deposits, but most of them are unable to cross blood-brain barrier, due to its low lipophilicity or present the permanent charge in their structures. Therefore, there is strong motivation to develop suitable compounds for in vitro fibril quantitation as well as for in vivo amyloid imaging.
Methods: In this study, we synthesized some novel barbituric and benzothiazole compounds and examine their potential property to quantitatively detect the amyloid fibrils of some non-disease related amyloidogenic proteins in comparison with native soluble proteins or amorphous aggregation.
Results: Our results showed that some of the synthesized compounds could selectively and specifically bind to amyloid fibrils while other compounds demonstrated a low-affinity binding. Furthermore, our synthesized compounds due to neutral charge and high lipophilicity essence might cross the BBB and detect the amyloid fibril in vivo.
Conclusion: These synthesized compounds based on selectivity and specificity parameters showed high binding affinity to amyloid fibrils in dye-binding studies. Uncharged barbituric/ thiobarbituric acid derivatives are supposed to cross the BBB. Hence, such dyes with better lipophilicity and without permanent positive charge can be a suitable candidate as a probe for early diagnosis to detect the amyloid plaque in neurodegenerative disease.
Keywords: Amyloid determination, Amyloid fibril, Neurodegenerative disease