Chemical synthesis, biological activities, and molecular simulations of novel sulfonylurea compounds bearing ortho-alkoxy substitutions

Abstract

A series of 51 novel sulfonylurea compounds with ortho-alkoxy substituent at phenyl ring were chemically synthesized and spectroscopically characterized. The biological activities of the target compounds were evaluated using the enzyme inhibition against acetohydroxyacid synthase (AHAS; EC 2.2.1.6) from fungal or plant source, as well as cell-based antifungal assay and greenhouse pot herbicidal assay. Among the target compounds, 6e showed desirable antifungal activity against Candida albicans standard isolate sc5314 with minimum inhibition concentration (MIC) of 0.39 mg/L (0.98 μM) after 24 h, and 6a demonstrated promising pre-emergence herbicidal activity against Echinochloacrus-galli at 30 g/ha dosage. Representative compounds 6a, 6e, and 6i showed no cell cytotoxicity even at 40 mg/L concentration. Theoretical DFT calculations indicated HOMO maps should be considered to understand the structure-activity relationships. The present study has hence provided useful information for further discovery of novel antifungal agents or selective herbicides.

Keywords: AHAS; antifungal activity; herbicidal activity; molecular simulation; sulfony lurea.