Review on some polyphenolic compounds including aurone derivative as a remarkable probe to identify AD amyloid plaque aggregations

Review on some polyphenolic compounds including aurone derivative as a remarkable probe to identify AD amyloid plaque aggregations
Sirvan Abbasbeigi,^1,* Reza khodarahmi,² Hadi Adibi,³ Sirous Ghobadi,⁴
1. Medical biology research center, Kermanshah university of medical sciences, Kermanshah, Iran
2. Medical biology research center, Kermanshah university of medical sciences, Kermanshah, Iran
3. Faculty of pharmacy, Kermanshah university of medical sciences, Kermanshah, Iran
4. Department of biochemistry, Faculty of fundamental sciences, Razi university, Kermanshah, Iran
Introduction: We have reported that aurone derivatives are a class of polyphenols which assumed that could bind to neurofibrillary tangle structures in vivo in contrast with other probes such as ThT and ThS. Therefore it is required to examine in vitro because of its positive charge and low lipophilicity coefficient. The recent criteria have explained the disability of Thioflavin T/S to cross the blood-brain barrier and identify amyloid aggregated properly. On the other hand, we synthesized a group of the compound base on the aurone core structure. Meanwhile, we have chosen a natural core structure came from polyphenols group and enable the synthetic compound to detect amyloid aggregates specifically and selectively considering the lack of positive charge and low lipophilicity related to compounds, which was mentioned previously.
Methods: We have provided three different conditions to make a comparison for each compound to identify several parameters of examination. Beta Lacto globin as an all bête secondary structure, Bovine serum albumin as a mixture of alpha/beta secondary structure and eventually globin as all secondary alpha structure. The above-mentioned parameters prepare various circumstances had to be evaluated for each type of compound in addition to a standard probe like Thioflavin T. In another word we have investigated each kind of our synthetic compound in the three different conditions plus a standard amyloid detector to illustrate the strength and weakness of each one respectively. In the following study, we have added new date associated with Atomic force microscopy, Transmission electron microscopy, antioxidant activity, and also computer molecular modeling.
Results: Since first, it was evident that the standard detector can demonstrate much better performance compared with the aurone synthetic compounds as it is shown in the Scatchard plot. However, the point is that the core structure of our compounds do not follow by the positive charge as well as Thioflavin T whereas their lipophilicity coefficient has displayed the proper numbers compared with Thioflavin T. Additionally, some compounds have presented high affinity to attach amyloid aggerates instead of Thioflavin T; While, they had no affinity to native secondary structure of protein which means high sensitivity compared with standard probe.
Conclusion: In conclusion, the previous have suggested that polyphenolic compounds from food products may be useful in targeting Aβ. Among all of them, flavonoids have been interested due to their antioxidant, anti-inflammation properties, targeting metal-Aβ40 aggregation invitro and diminish cytotoxicity induced by metal-Aβ40. Recently, it was reported that flavonoids, including flavones and aurone, serve as a useful molecular probe in the development of imaging agents for β-amyloid plaques in the brain. To explore more useful candidate for amyloid imaging probes, we selected one of the flavonoids, aurone, as a new core structure.
Keywords: Polyphenolic compounds, Amyloid aggregations, Protein disorders, Alzheimer's disease,