Submit Manuscript  

Article Details


New Research for Quinazoline-2,4-diones as HPPD Inhibitors Based on 2D-MLR and 3D-QSAR Models

Author(s):

Ying Fu, Yi-Na Sun, Hai-Feng Cao, Ke-Han Yi, Li-Xia Zhao, Jia-Zhong Li and Fei Ye  

Abstract:


4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting p-hydroxyphenylpyruvate to homogentisate, is an important target for treating type I tyrosinemia and synthesizing novel herbicides due to its significant role in tyrosine catabolism. HPPD inhibitors, sulcotrione, mesotrione and benzobicylon etc. have been used in commercialized herbicides by binding to HPPD. Based on the structure-activity relationships, a series of quinolinone-2,4-diones derivatives were studied using combined of 2D-MLR and 3D-QSARand the structural requirements for their HPPD inhibition have been investigated.. All models demonstrated satisfying results through internal and external validation, especially good predictive abilities. To intuitively understand the relationship between structure and activity of molecules, the CoMFA and CoMSIA contour maps showed vital structural characteristics related to HPPD inhibitors activities. The contribution of steric, electrostatic, hydrogen donor and acceptor from the contour maps could be visualized. These results provided a valuable tool for designing novel HPPD inhibitors with better biological activity in the future.

Keywords:

HPPD inhibitor, 2D-MLR, pharmacophore, CoMFA, CoMSIA.

Affiliation:

Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin, 150030, Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin, 150030, Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin, 150030, Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin, 150030, Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin, 150030, School of Pharmacy, Lanzhou University, 199 West Donggang Rd., 730000 Lanzhou, Department of Applied Chemistry, College of Science, Northeast Agricultural University, Harbin, 150030



Full Text Inquiry