3-Tetrazolyl-β-carboline derivatives as potential neuroprotective agents

IF 3.3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic & Medicinal Chemistry Pub Date : 2024-07-18 DOI:10.1016/j.bmc.2024.117841

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Abstract

3-Tetrazolyl-β-carbolines were prepared by the Pictet-Spengler approach using a tryptophan analogue as building block, in which the carboxylic acid was replaced by the bioisosteric tetrazole group. Knowing that β-carbolines are often associated with psychopharmacological effects, the study of the 3-tetrazolyl-β-carbolines as potential neuroprotective agents against Parkinson’s disease was investigated. The evaluation of neuroprotective effects against 1-methyl-4-phenylpyridin-1-ium (MPP⁺)-induced cytotoxicity allowed to identify compounds with relevant neuroprotective activity. One derivative, 3-(1-benzyl-1H-tetrazol-5-yl)-1-(p-dimethylaminophenyl)-β-carboline, stood out for its low cytotoxicity and excellent performance, preventing cell death induced by this neurotoxin. The most promising compounds were also evaluated for their neuroprotective properties against iron (III)-induced cytotoxicity. However, only one 3-tetrazolyl-β-carboline derivative slightly reduced iron-induced cytotoxicity. Overall, the neuroprotective properties of 3-tetrazolyl-β-carbolines have been demonstrated and this finding may contribute to the development of new therapies for Parkinson’s disease.

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作为潜在神经保护剂的 3-四唑基-β-咔啉衍生物

3-Tetrazolyl-β-carbolines 以色氨酸类似物为结构单元，通过 Pictet-Spengler 方法制备，其中的羧酸被生物异构的四唑基团取代。了解到 β-咔啉通常与精神药理作用有关，研究人员对 3-四唑基-β-咔啉作为潜在的帕金森病神经保护剂进行了研究。通过评估对 1-甲基-4-苯基吡啶-1-鎓（MPP+）诱导的细胞毒性的神经保护作用，确定了具有相关神经保护活性的化合物。其中一种衍生物，即 3-（1-苄基-1H-四唑-5-基）-1-（对二甲氨基苯基）-β-咔啉，因其细胞毒性低且性能卓越而脱颖而出，可防止这种神经毒素诱导的细胞死亡。此外，还评估了最有前途的化合物对铁（III）诱导的细胞毒性的神经保护特性。然而，只有一种 3-四唑基-β-咔啉衍生物能轻微降低铁诱导的细胞毒性。总之，3-四唑基-β-咔啉类化合物具有神经保护特性，这一发现可能有助于开发治疗帕金森病的新疗法。

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来源期刊

Bioorganic & Medicinal Chemistry 医学-生化与分子生物学

CiteScore

6.80

自引率

2.90%

发文量

413

审稿时长

17 days

期刊介绍： Bioorganic & Medicinal Chemistry provides an international forum for the publication of full original research papers and critical reviews on molecular interactions in key biological targets such as receptors, channels, enzymes, nucleotides, lipids and saccharides. The aim of the journal is to promote a better understanding at the molecular level of life processes, and living organisms, as well as the interaction of these with chemical agents. A special feature will be that colour illustrations will be reproduced at no charge to the author, provided that the Editor agrees that colour is essential to the information content of the illustration in question.