Targeting PDGF receptor inhibitors: synthesis and biological evaluation of oleanolic acid analogs
10.16438/j.0513-4870.2018-0806
- VernacularTitle:靶向PDGF受体抑制剂的齐墩果酸类似物合成及其抗肿瘤生物活性研究
- Author:
Qian-wen LI
1
;
Zhen-yu KUAI
1
;
Xiao-xiao LI
1
;
Chuan-dong XU
1
;
Yan-qiu MENG
1
Author Information
1. Department of Pharmaceutical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
oleanolic acid derivatives;
structural modification;
computer aided design
- From:
Acta Pharmaceutica Sinica
2018;53(12):2076-2084
- CountryChina
- Language:Chinese
-
Abstract:
The computer-aided design was used to simulate the docking of PDGF receptor with known active compounds, and the active groups that can bind to key sites were identified by analyzing the key amino acid residue fragments that exerted active effects on the target proteins. The natural product oleanolic acid was used as the parent, and the active group was introduced into the 2-position, and the C-28 carboxyl group was esterified and amidated. A series of oleanolic acid analogues targeting PDGF receptor inhibitors were designed and synthesized. Their structures were confirmed by MS and NMR. Through MTT assay, SGC-7901 and A549 cells were selected for preliminary in vitro anti-tumor activity screening. PDGF receptor protein inhibition test was performed on I3 and Ⅱ5 by FPIA. The activity tests showed that I3 and Ⅱ5, compared with the positive control drug, had stronger inhibition. FPIA test showed that Ⅱ5 and PDGF receptor protein had good binding ability. The newly synthesized oleanolic acid analogues have significantly higher antitumor activity than the parent compound and deserve further study.
