Design and synthesis of further simplified pyripyropene A based ACAT2 selective inhibitors

Yi Liu; Xiaowei Zhang; Yang Zhan; Boliang Li; Wei Lu; Fajun Nan

doi:10.1016/j.tet.2019.01.017

Design and synthesis of further simplified pyripyropene A based ACAT2 selective inhibitors

Yi Liu
, Xiaowei Zhang
, Yang Zhan
, Boliang Li
, Wei Lu
, Fajun Nan^*

^*此作品的通讯作者

化学与分子工程学院

East China Normal University
CAS - Center for Excellence in Molecular Cell Science
CAS - Shanghai Institute of Materia Medica

科研成果: 期刊稿件 › 文章 › 同行评审

3 引用（Scopus）

摘要

Acyl-coenzyme A: cholesterol acyltransferases (ACATs) play the significant role in the formation of cholesterol esters. One form of this enzyme is ACAT2, which not only regulates the balance of cholesterol metabolism in cells but also participates in the “escape” mechanism of hepatocellular carcinoma (HCC) cells. The natural product pyripyropene A (PPPA) and its analogs are the only chemical ACAT2-specific inhibitors. To develop simpler analogs and endeavor to remove a portion of multichiral centers and enrich a variety of analogs, new PPPA analogs are creatively designed and synthesized based on previous work. Among these new analogs, 7a and 9f show better activity and selective inhibition of ACAT2 compared with PPPA. These results will provide a new future for potential therapeutic use in atherosclerosis and HCC.

源语言	英语
页（从-至）	1819-1825
页数	7
期刊	Tetrahedron
卷	75
期	12
DOI	https://doi.org/10.1016/j.tet.2019.01.017
出版状态	已出版 - 22 3月 2019

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10.1016/j.tet.2019.01.017

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title = "Design and synthesis of further simplified pyripyropene A based ACAT2 selective inhibitors",

abstract = "Acyl-coenzyme A: cholesterol acyltransferases (ACATs) play the significant role in the formation of cholesterol esters. One form of this enzyme is ACAT2, which not only regulates the balance of cholesterol metabolism in cells but also participates in the “escape” mechanism of hepatocellular carcinoma (HCC) cells. The natural product pyripyropene A (PPPA) and its analogs are the only chemical ACAT2-specific inhibitors. To develop simpler analogs and endeavor to remove a portion of multichiral centers and enrich a variety of analogs, new PPPA analogs are creatively designed and synthesized based on previous work. Among these new analogs, 7a and 9f show better activity and selective inhibition of ACAT2 compared with PPPA. These results will provide a new future for potential therapeutic use in atherosclerosis and HCC.",

keywords = "Acyl-coenzyme A, Cholesterol acyltransferase 2 selective inhibitors, Pyripyropene A, Simplified structure",

author = "Yi Liu and Xiaowei Zhang and Yang Zhan and Boliang Li and Wei Lu and Fajun Nan",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = mar,

day = "22",

doi = "10.1016/j.tet.2019.01.017",

language = "英语",

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pages = "1819--1825",

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TY - JOUR

T1 - Design and synthesis of further simplified pyripyropene A based ACAT2 selective inhibitors

AU - Liu, Yi

AU - Zhang, Xiaowei

AU - Zhan, Yang

AU - Li, Boliang

AU - Lu, Wei

AU - Nan, Fajun

PY - 2019/3/22

Y1 - 2019/3/22

N2 - Acyl-coenzyme A: cholesterol acyltransferases (ACATs) play the significant role in the formation of cholesterol esters. One form of this enzyme is ACAT2, which not only regulates the balance of cholesterol metabolism in cells but also participates in the “escape” mechanism of hepatocellular carcinoma (HCC) cells. The natural product pyripyropene A (PPPA) and its analogs are the only chemical ACAT2-specific inhibitors. To develop simpler analogs and endeavor to remove a portion of multichiral centers and enrich a variety of analogs, new PPPA analogs are creatively designed and synthesized based on previous work. Among these new analogs, 7a and 9f show better activity and selective inhibition of ACAT2 compared with PPPA. These results will provide a new future for potential therapeutic use in atherosclerosis and HCC.

AB - Acyl-coenzyme A: cholesterol acyltransferases (ACATs) play the significant role in the formation of cholesterol esters. One form of this enzyme is ACAT2, which not only regulates the balance of cholesterol metabolism in cells but also participates in the “escape” mechanism of hepatocellular carcinoma (HCC) cells. The natural product pyripyropene A (PPPA) and its analogs are the only chemical ACAT2-specific inhibitors. To develop simpler analogs and endeavor to remove a portion of multichiral centers and enrich a variety of analogs, new PPPA analogs are creatively designed and synthesized based on previous work. Among these new analogs, 7a and 9f show better activity and selective inhibition of ACAT2 compared with PPPA. These results will provide a new future for potential therapeutic use in atherosclerosis and HCC.

KW - Acyl-coenzyme A

KW - Cholesterol acyltransferase 2 selective inhibitors

KW - Pyripyropene A

KW - Simplified structure

UR - https://www.scopus.com/pages/publications/85060103945

U2 - 10.1016/j.tet.2019.01.017

DO - 10.1016/j.tet.2019.01.017

M3 - 文章

AN - SCOPUS:85060103945

SN - 0040-4020

VL - 75

SP - 1819

EP - 1825

JO - Tetrahedron

JF - Tetrahedron

IS - 12

ER -

Design and synthesis of further simplified pyripyropene A based ACAT2 selective inhibitors

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