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Screen of pseudopeptidic inhibitors of human sirtuins 1-3: two lead compounds with antiproliferative effects in cancer cells.

Abstract：

:In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis, aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to reveal their in vitro inhibition activities. Molecular modeling studies were performed to acquire data about the binding modes of the inhibitors. Three sirtuin inhibitors were subjected to cellular studies, and all of them showed an increase in acetylation of Lys382 of p53 after DNA damage. Furthermore, two of the compounds were able to inhibit both A549 lung carcinoma and MCF-7 breast carcinoma cell growth in micromolar concentration with the ability to arrest cancer cell cycle in the G1 phase.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Mellini P,Kokkola T,Suuronen T,Salo HS,Tolvanen L,Mai A,Lahtela-Kakkonen M,Jarho EM

doi

10.1021/jm400438k

subject

Has Abstract

pub_date

2013-09-12 00:00:00

pages

6681-95

issue

17

eissn

0022-2623

issn

1520-4804

journal_volume

56

pub_type

杂志文章

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