resistance to anticancer drugs. The aim of this study was to design, synthesize and develop new potent and selective inhibitors of BCRP that can be used to abolish MDR and potentialize clinically used anticancer agents. In previous reports, we showed the importance of chromone scaffold and hydrophobicity for the inhibition of ABC transporters. In the present study we report the design and development
Substituted Chromones as Highly Potent Nontoxic Inhibitors, Specific for the Breast Cancer Resistance Protein
作者:Glaucio Valdameri、Estelle Genoux-Bastide、Basile Peres、Charlotte Gauthier、Jérôme Guitton、Raphaël Terreux、Sheila M. B. Winnischofer、Maria E. M. Rocha、Ahcène Boumendjel、Attilio Di Pietro
DOI:10.1021/jm201404w
日期:2012.1.26
and low cytotoxicity, giving a markedly high therapeutic index. The chromone derivative specifically inhibited ABCG2 versus other multidrug ABC transporters and was not transported. It constitutes a highly promising candidate for in vivo chemosensitization of ABCG2-expressing tumors.
Selected chromone derivatives as inhibitors of monoamine oxidase
作者:Lesetja J. Legoabe、Anél Petzer、Jacobus P. Petzer
DOI:10.1016/j.bmcl.2012.07.025
日期:2012.9
A previous study has shown that a series of C6-benzyloxy substituted chromones exhibit high binding affinities for human monoamine oxidase (MAO) B. In an attempt to discover additional chromones with potent and selective MAO-B inhibitory potencies and to further examine the structure-activity relationships of MAO-B inhibition by chromones, the series was expanded with homologues containing polar functional groups on C3 of the chromone ring. The results demonstrate that 6-[(3-bromobenzyl)oxy] chromones containing acidic and aldehydic functional groups on C3 act as potent reversible MAO-B inhibitors with IC50 values of 2.8 and 3.7 nM, respectively. Interestingly, a 2-hydroxy-2,3-dihydro-1-benzopyran-4-one derivative as well as open-ring 2-acetylphenol analogues of the chromones also were potent MAO-B inhibitors with IC50 values ranging from 4 to 11 nM. Chromone derivatives containing the benzyloxy substituent on C5 of the chromone ring, however, exhibit MAO-B inhibition potencies that are several orders of magnitude weaker. High potency inhibitors of MAO-B may find application in the therapy of neurodegenerative disorders such as Parkinson's disease. (C) 2012 Elsevier Ltd. All rights reserved.