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链支化多羟基八氢吲哚作为治疗溶酶体贮积症的潜在先导化合物

Chain-Branched Polyhydroxylated Octahydro--Indoles as Potential Leads against Lysosomal Storage Diseases.

作者信息

Estévez Juan C, González Marcos A, Villaverde M Carmen, Hirokami Yuki, Kato Atsushi, Sussman Fredy, Reza David, Estévez Ramón J

机构信息

Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

Departamento de Química Orgánica, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

出版信息

Pharmaceuticals (Basel). 2019 Mar 29;12(2):47. doi: 10.3390/ph12020047.

DOI:10.3390/ph12020047
PMID:30934879
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6631223/
Abstract

Here, the synthesis and glycosidase inhibition properties of the two first known 3-ethyloctahydro-1-indole-4,5,6-triols are reported. This study shows the transformation of d-glucose into polyhydroxylated 1-(2-nitrocyclohexane) acetaldehydes, followed by a protocol involving the formation of the azacyclopentane ring. Results of inhibitory potency assays and docking calculations show that at least one of them could be a lead for optimization in the search for compounds that behave like folding chaperones in lysosomal storage diseases.

摘要

本文报道了两种首次发现的3-乙基八氢-1-吲哚-4,5,6-三醇的合成及其糖苷酶抑制特性。该研究展示了将d-葡萄糖转化为多羟基化的1-(2-硝基环己烷)乙醛，随后通过一个涉及氮杂环戊烷环形成的方案。抑制活性测定和对接计算结果表明，其中至少一种化合物可能成为优化筛选在溶酶体贮积病中发挥折叠伴侣作用的化合物的先导物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/c7ffcff5a11c/pharmaceuticals-12-00047-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/56055290fc29/pharmaceuticals-12-00047-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/bd5a451f33cb/pharmaceuticals-12-00047-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/234c3c9acfda/pharmaceuticals-12-00047-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/6c4e599bc05e/pharmaceuticals-12-00047-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/6ae24afdddc7/pharmaceuticals-12-00047-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/0f27327c6d64/pharmaceuticals-12-00047-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/c7ffcff5a11c/pharmaceuticals-12-00047-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/56055290fc29/pharmaceuticals-12-00047-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/bd5a451f33cb/pharmaceuticals-12-00047-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/234c3c9acfda/pharmaceuticals-12-00047-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/6c4e599bc05e/pharmaceuticals-12-00047-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/6ae24afdddc7/pharmaceuticals-12-00047-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/0f27327c6d64/pharmaceuticals-12-00047-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af20/6631223/c7ffcff5a11c/pharmaceuticals-12-00047-g005.jpg

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