Identification of (beta-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor gamma activity
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초록

We applied an improved virtual screening scheme combining ligand-centric and receptor-centric methods for the identification of a new series of PPAR gamma agonists known as (beta-carboxyethyl)-rhodanine derivatives which include a thiazolidin-based core structure, 2-thioxo-thiazolidine-4-one. An in vitro assay confirmed the nanomolar binding affinity in one of the (beta-carboxyethyl)-rhodanine derivatives, SP1818. It showed a PPAR gamma agonistic activity similar to that of a known PPAR gamma drug, pioglitazone, in a cell-based transactivation assay. Furthermore, the structure-activity relationships of the rhodanine derivatives were investigated through comparative molecular field analysis. We also characterized the inconsistency between the in vitro binding affinity and cell-based transactivation ability by using a set of property-based molecular descriptors. The binding mode analysis provided new insight concerning their agonistic effect on PPAR gamma. (C) 2009 Elsevier Masson SAS. All rights reserved.

키워드

RhodaninePeroxisome proliferators-activated receptor (PPAR)Thiazolidinedione (TZD)Computer-aided drug discovery, Molecular docking, Binding mode analysisMOLECULAR-FIELD ANALYSISRHODANINE DERIVATIVESLIGAND-BINDINGPPAR-GAMMAMETABOLIC DISEASECANCER CELLSCOMFAINHIBITORSAGONISTSALPHA
제목
Identification of (beta-carboxyethyl)-rhodanine derivatives exhibiting peroxisome proliferator-activated receptor gamma activity
저자
Choi, JiwonKo, YoonaeLee, Hui SunPark, Yun SunYang, YoungYoon, Sukjoon
DOI
10.1016/j.ejmech.2009.09.042
발행일
2010-01
유형
Article
저널명
European Journal of Medicinal Chemistry
45
1
페이지
193 ~ 202