Targeting Photosystem II: Design and Synthesis of 4,6-Diarylpyrimidin-2(1H)-thione Derivatives

Resumo

This study describes the synthesis of 4,6-diarylpyrimidin-2(1H)-thione derivatives and their evaluation as potential inhibitors of photosystem II (PSII) through chlorophyll a fluorescence assays and molecular docking studies. Compounds 4,6-diphenyl-3,4-dihydropyrimidine-2(1H)-thione and 6-(4-bromophenyl)-4-phenyl-3,4-dihydropyrimidine-2(1H)-thione decreased the performance index on an absorption basis by 74% and 65%, respectively, and reduced electron transport per reaction center by 17% and 30% compared to the negative control. These effects demonstrate an impairment of the PSII electron transport chain. Docking simulations using the D1 protein subunit of PSII (PDB ID: 4V82) revealed that stereochemistry influences binding affinity and interaction profiles. The S-enantiomers formed stronger hydrogen bonds with key residues such as His215 and exhibited enhanced hydrophobic and π–π interactions within the active site. Overall, the results highlight the 4,6-diarylpyrimidin-2(1H)-thione scaffold as a promising lead for development of novel herbicidal agents targeting PSII, while underscoring the value of integrating molecular and physiological approaches to support future structure-based optimization.