| Synthesis and biological evaluation of thio-benzodiazepines as novel small molecule inhibitors of the p53-MDM2 protein-protein interaction. | |
| | |
MedLine Citation:
|
PMID: 21996465 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
A series of thio-benzodiazepine p53-MDM2 inhibitors were designed and synthesized based on the principle of bioisosterism. Most of the thio-benzodiazepines had nanomolar to micromolar affinity toward MDM2. Particularly, compounds 8a (K(i) = 0.52μM) and 8f (K(i) = 0.32μM) showed binding activity comparable to the positive drug nutlin-3a (K(i) = 0.23μM). Meanwhile, compound 8j exhibited excellent antitumor activity against the U-2 OS human osteosarcoma cell line with an IC(50) value of 1.06μM, which was about 23 times higher than that of nutlin-3a. The docking model also successfully predicted that this class of compounds mimicked three p53 critical residues binding to MDM2. The thio-benzodiazepines represent a promising class of non-peptide inhibitors of the p53-MDM2 interaction. |
| | |
Authors:
|
Chunlin Zhuang; Zhenyuan Miao; Lingjian Zhu; Yongqiang Zhang; Zizhao Guo; Jianzhong Yao; Guoqiang Dong; Shengzheng Wang; Yang Liu; Hai Chen; Chunquan Sheng; Wannian Zhang |
Related Documents
:
|
8755745 - Histidine-450 is the catalytic residue of l-3-hydroxyacyl coenzyme a dehydrogenase asso... 12493825 - A structural basis for the mechanism of aspartate-beta-semialdehyde dehydrogenase from ... 15689995 - Biochemistry: role of pqq as a mammalian enzyme cofactor? 18453685 - The structures of alcaligenes faecalis d-3-hydroxybutyrate dehydrogenase before and aft... 8609635 - Three htim mutants that provide new insights on why tim is a dimer. 3815405 - Structural studies of a polysaccharide (s-88) elaborated by pseudomonas atcc 31554. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-10-2 |
Journal Detail:
|
Title: European journal of medicinal chemistry Volume: - ISSN: 1768-3254 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
|
Created Date: 2011-10-14 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0420510 Medline TA: Eur J Med Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011. Published by Elsevier Masson SAS. |
Affiliation:
|
School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The ascorbyl palmitate-polyethyleneglycol 400-water system phase behavior.
Next Document: 1-Aryl-5-(1H-pyrrol-1-yl)-1H-pyrazole-3-carboxamide: An effective scaffold for the design of either ...