Synthesis and biological evaluation of phosphoinositide 3-kinase (PI3K) inhibitors based on a quinoxaline scaffold
10.16438/j.0513-4870.2019-0679
- VernacularTitle:基于喹喔啉为母核的PI3K抑制剂的合成及抗肿瘤活性研究
- Author:
Tao HUANG
1
;
Hui-fang LAI
2
;
Rong-kun LIN
2
;
Jin LIN
2
;
Zhu-lai LI
2
;
Xiu-zhi XU
2
Author Information
1. Fujian Provincial Children's Hospital (Fujian Provincial Maternity and Children's Hospital), Fuzhou 350001, China; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, College of Pharmacy, Fujian Medical University, Fuzhou 350122, China
2. Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, College of Pharmacy, Fujian Medical University, Fuzhou 350122, China
- Publication Type:Research Article
- Keywords:
quinoxaline derivative;
anti-tumour;
PI3K inhibitor
- From:
Acta Pharmaceutica Sinica
2020;55(1):96-105
- CountryChina
- Language:Chinese
-
Abstract:
Based on the structure of inhibitors XL765 and WR23, the quinoxaline scaffold was selected as an attractive structure for drug design. In this protocol, the 2-position of quinoxaline was modified with a substituted phenoxy fragment. Meanwhile, the linking chain at the 3-position was changed to a sulfonyl hydrazine or was removed. A series of substituent groups were added at the 6-position of the quinoxaline scaffold. Twenty-two quinoline derivatives were designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR, and ESI-MS. All compounds were screened for anti-tumor activity in vitro in A549, MCF-7, HCT-116 and HepG2 cancer cells. The results showed that P6b was effective, P6e and P6f had better activity against HCT116 (IC50 = 3.24, 4.78 and 4.50 μmol·L-1), and P6d had strong inhibitory effect on MCF-7 (IC50 = 0.228 7 μmol·L-1).
