Structure-activity relationship analysis of novel farnesyl transferase inhibitors
10.16438/j.0513-4870.2018-0823
- VernacularTitle:新型法尼基转移酶抑制剂的发现及构效关系分析
- Author:
Ming ZHANG
1
;
Shi-liang LI
1
;
Li-li ZHU
1
;
Jin HUANG
1
;
Zhen-jiang ZHAO
1
;
Hong-lin LI
1
Author Information
1. Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
- Publication Type:Research Article
- Keywords:
farnesyltransferase;
inhibitor;
virtual screening;
structure-activity relationship
- From:
Acta Pharmaceutica Sinica
2019;54(1):111-116
- CountryChina
- Language:Chinese
-
Abstract:
Farnesyltransferase (FTase) was selected as a target for virtual screening of inhibitors using the Glide v4.0 program in the Schrödinger software package. We discovered 13 novel structures as farnesyltransferase inhibitors (FTIs) with moderate potency. By analyzing the binding modes of representative compounds 8 (IC50 = 2.29 μmol·L-1) and 18 (IC50 = 0.41 μmol·L-1) with farnesyltransferase, it was found that compounds 8 and 18 didn't coordinate with Zn2+, indicating that the coordination between FTIs with Zn2+ is not essential for the bioactivity of the inhibitors. The structure-activity relationship was summarized by analyzing the predicted binding modes of representative compounds. It was found that the scaffolds of the discovered FTIs had room for structural optimization, which lay foundation for obtaining highly active and selective FTIs.
