التفاصيل البيبلوغرافية
| العنوان: |
Multifunctional agents against Alzheimer's disease based on oxidative stress: Polysubstituted pyrazine derivatives synthesized by multicomponent reactions. |
| المؤلفون: |
Wei, Wenxiu1 (AUTHOR), Jing, Lanlan1 (AUTHOR), Tian, Ye1,2 (AUTHOR) yetian@sdu.edu.cn, Więckowska, Anna3 (AUTHOR), Kang, Dongwei1 (AUTHOR), Meng, Bairu1 (AUTHOR), Panek, Dawid3 (AUTHOR), Godyń, Justyna3 (AUTHOR), Góral, Izabella3 (AUTHOR), Song, Yuning1,4 (AUTHOR) syncat827@163.com, Liu, Xinyong1 (AUTHOR) xinyongl@sdu.edu.cn, Zhan, Peng1 (AUTHOR) zhanpeng1982@sdu.edu.cn |
| المصدر: |
Bioorganic & Medicinal Chemistry. Dec2023, Vol. 96, pN.PAG-N.PAG. 1p. |
| مصطلحات موضوعية: |
*ALZHEIMER'S disease, *OXIDATIVE stress, *PYRAZINES, *CHEMICAL synthesis, *NEURODEGENERATION, *DRUG efficacy |
| مستخلص: |
[Display omitted] • Passerini-3CR and Ugi-4CR proved to be an effective strategy for constructing multifunctional anti-AD agents. • Target compounds could be multifunctional anti-AD agents based on oxidative stress processes. • A3B3C1 exhibited versatility in antioxidant, Aβ 1-42 reduction and neuroprotection, which is deserve further development. As Alzheimer's disease (AD) is a neurodegenerative disease with a complex pathogenesis, the exploration of multi-target drugs may be an effective strategy for AD treatment. Multifunctional small molecular agents can be obtained by connecting two or more active drugs or privileged pharmacophores by multicomponent reactions (MCRs). In this paper, two series of polysubstituted pyrazine derivatives with multifunctional moieties were designed as anti-AD agents and synthesized by Passerini-3CR and Ugi-4CR. Since the oxidative stress plays an important role in the pathological process of AD, the antioxidant activities of the newly synthesized compounds were first evaluated. Subsequently, selected active compounds were further screened in a series of AD-related bioassays, including Aβ 1-42 self-aggregation and deaggregation, BACE-1 inhibition, metal chelation, and protection of SH-SY5Y cells from H 2 O 2 -induced oxidative damage. Compound A3B3C1 represented the best one with multifunctional potencies. Mechanism study showed that A3B3C1 acted on Nrf2/ARE signaling pathway, thus increasing the expression of related antioxidant proteins NQO1 and HO-1 to normal cell level. Furthermore, A3B3C1 showed good in vitro human plasma and liver microsome stability, indicating a potential for further development as multifunctional anti-AD agent. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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