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硼基杂化物作为开发具有神经保护特性药物的新型支架。

Boron-based hybrids as novel scaffolds for the development of drugs with neuroprotective properties.

作者信息

Cacciatore Ivana, Turkez Hasan, Di Rienzo Annalisa, Ciulla Michele, Mardinoglu Adil, Di Stefano Antonio

机构信息

Department of Pharmacy, University "G. d'Annunzio" of Chieti-Pescara via dei Vestini 31 66100 Chieti Scalo CH Italy

Faculty of Science, Basic Medical Sciences, Medical Biology Department, Ataturk University 25240 Yakutiye Erzurum Turkey.

出版信息

RSC Med Chem. 2021 Aug 13;12(11):1944-1949. doi: 10.1039/d1md00177a. eCollection 2021 Nov 17.

Abstract

Novel boron-based compounds (BBCs) were synthesized and evaluated as potential candidates for the development of novel drugs against Alzheimer's disease (AD). The neuroprotective profile of novel BBCs was evaluated using Aβ1-42-treated-SH-SY5Y cells while their antioxidant activity was evaluated by total antioxidant capacity (TAC) and total oxidative status (TOS) assays. Results showed that (a novel boron-based hybrid containing an antioxidant portion) inhibited cell death induced by Aβ1-42-exposure in differentiated SH-SY5Y cells, resulting in an increase in cell viability by 25-33% (MTT assay) and by 63-71% (LDH assay) in a concentration range of 25-100 μM. Antioxidant assays demonstrated a good capability of to counteract the oxidative status. Moreover, possessed a significant ability to inhibit acetylcholinesterase (AChE) (22.96% at 50 μM), an enzyme whose enzymatic activity is increased in AD patients. In the present work, absorption and distribution properties of boron-based hybrids were predicted using Pre-ADMET software. preliminary results suggested that boron-based hybrids could be new structural scaffolds for the development of novel drugs for the management of AD.

摘要

合成了新型硼基化合物(BBCs),并将其评估为开发抗阿尔茨海默病(AD)新药的潜在候选物。使用经Aβ1-42处理的SH-SY5Y细胞评估新型BBCs的神经保护作用,同时通过总抗氧化能力(TAC)和总氧化状态(TOS)测定评估其抗氧化活性。结果表明,(一种含有抗氧化部分的新型硼基杂化物)在分化的SH-SY5Y细胞中抑制了由Aβ1-42暴露诱导的细胞死亡,在25-100μM的浓度范围内,通过MTT法使细胞活力提高了25-33%,通过LDH法使细胞活力提高了63-71%。抗氧化测定表明,该化合物具有良好的对抗氧化状态的能力。此外,该化合物具有显著的抑制乙酰胆碱酯酶(AChE)的能力(在50μM时为22.96%),该酶在AD患者中的酶活性会增加。在本研究中,使用Pre-ADMET软件预测了硼基杂化物的吸收和分布特性。初步结果表明,硼基杂化物可能是开发用于治疗AD的新药的新结构支架。

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