Computer-Aided and AILDE Approaches to Design Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

ABSTRACT: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a pivotal enzyme in tocopherol and plastoquinone synthesis and a potential target for novel herbicides. Thirty-five pyridine derivatives were selected to establish a Topomer comparative molecular field analysis (Topomer CoMFA) model to obtain correlation information between HPPD inhibitory activity and the molecular structure. A credible and predictive Topomer CoMFA model was established by "split in two R-groups" cutting methods and fragment combinations (q² = 0.703, r² = 0.957, ONC = 6). The established model was used to screen out more active compounds and was optimized through the auto in silico ligand directing evolution (AILDE) platform to obtain potential HPPD inhibitors. Twenty-two new compound

SUBMITTER: Shi J 

PROVIDER: S-EPMC9320391 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature