oa Highly Efficient and Eco-friendly Synthesis and Bio-activities of 1,3-benzazoles as Cu (II) Chelators in Alzheimer’s Disease Therapy

Dyshomeostasis of Cu²⁺ and abnormal interactions between Cu²⁺ and β Amyloid peptide (Aβ) can promote Aβ aggregation and oxidative stress, which are considered to trigger Alzheimer’s Disease (AD). Metal chelating therapy is a promising approach for the treatment of AD.

In this study, 2-(2-hydroxyphenyl)benzazoles were synthesized via microwave irradiation promotion. Chelators inhibiting Cu²⁺-induced Aβ aggregation were determined through turbidity assay and BCA protein assay, while anti-oxidants were detected via HRP/Amplex red assay and fluorescent probe of DCFH-DA. Cell viability was measured by MTT assay.

The bio-activity for inhibiting Cu²⁺ induced-Aβ aggregation of chelators S-1, S-3, S-4, S-5, S-7, S-10, N-5, N-9, N-10 O-2, O-4, X-N-2 was better than that of CQ. The ability of the chelators (S-1, S-10, O-2, O-5, N-9, and X-N-2) to decrease the level of ROS in Aβ+Cu²⁺ treated SH-SY5Y cells was better than that of CQ. The ability to attenuate Aβ-mediated cytotoxicity in SH-SY5Y cells of S-10 (O-2, O-5, and N-9) was better than that of CQ.

After the evolution of the bio-activities for the treatment of AD in vitro, it was found that 4 chelators (S-10, O-2, O-5, and N-9) exhibited better bio-activities than CQ in all aspects.