龙眼内酯类似物作为神经营养剂的合成及生物学评价

Synthesis and biological evaluation of longanlactone analogues as neurotrophic agents.

作者信息

Reddy Chada Raji, Tukaram Amol Gorgile, Mohammed Siddique Z, Dilipkumar Uredi, Babu Bathini Nagendra, Chakravarty Sumana, Bhattacharya Dwaipayan, Joshi Pranav C, Grée René

机构信息

Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.

National Institute of Pharmaceutical Education and Research, Hyderabad 500037 India.

出版信息

Bioorg Med Chem Lett. 2018 Feb 15;28(4):673-676. doi: 10.1016/j.bmcl.2018.01.020. Epub 2018 Jan 12.

DOI:10.1016/j.bmcl.2018.01.020

PMID:29402744

Abstract

Longanlactone analogues were synthesized using a route featuring Friedel-Crafts acylation, Sonogashira coupling and 1,3-dipolar cycloaddition reactions. Structure-activity relationships were investigated for neurotrophic activity. Compound 6 was found to have the most potent neurotrophic activity among all the synthesized analogues in Neuro2a cells as evidenced by a battery of in vitro/cell based assays for assessment of neurogenic and potential neurotrophic activity including neurite outgrowth assay and real time PCR for popular markers of augmented neurotrophic activity. Compound 6 might serve as a template for further development of highly effective neurotrophic molecules.

摘要

通过一条以傅克酰基化、Sonogashira偶联和1,3-偶极环加成反应为特征的路线合成了龙眼内酯类似物。研究了其对神经营养活性的构效关系。在Neuro2a细胞中，通过一系列基于体外/细胞的测定来评估神经发生和潜在的神经营养活性，包括神经突生长测定和针对增强神经营养活性的常用标志物的实时PCR，结果表明化合物6在所有合成类似物中具有最强的神经营养活性。化合物6可能作为进一步开发高效神经营养分子的模板。