Identifying novel selective PPO inhibitors through structure-based virtual screening and bio-evaluation.

ABSTRACT: Protoporphyrinogen oxidase (PPO) is a key enzyme in chlorophyll and heme biosynthesis, and the development of its inhibitors is of great importance both in the pharmaceutical and pesticide industries. However, the currently developed PPO inhibitors have insignificant bio-selectivity and have a serious impact on non-target organisms. In this study, a docking-based virtual screening approach combined with bio-activity testing was used to obtain novel selective inhibitors of PPO. The results of the bio-activity test showed that thirteen compounds showed 10-fold selectivity over human PPO. And the best selective compound, ZINC70338, has a K _i value of 2.21 μM for Nicotiana tabacum PPO and >113-fold selectivity for human PPO. The selectivity mechanism of ZINC70338 in di

SUBMITTER: Zhao SS 

PROVIDER: S-EPMC10075065 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature