State-Key Laboratory and Research Institute of Elemento-Organic Chemistry, National Pesticide Engineering Research Center, College of Chemistry, Nankai University, Tianjin, China.
School of Light Industry, Beijing Technology and Business University, Beijing, China.
Chem Biol Drug Des. 2022 Oct;100(4):487-501. doi: 10.1111/cbdd.14114. Epub 2022 Jul 14.
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.
一系列 51 种新型磺酰脲化合物被化学合成并进行了光谱表征，苯环上具有邻烷氧基取代基。目标化合物的生物活性通过对真菌或植物来源的乙酰羟酸合酶（AHAS；EC 2.2.1.6）的酶抑制活性、基于细胞的抗真菌测定和温室盆栽除草测定进行评估。在目标化合物中，化合物 6e 对白色念珠菌标准分离株 sc5314 显示出理想的抗真菌活性，在 24 小时后最小抑制浓度（MIC）为 0.39 mg/L（0.98 μM），化合物 6a 在 30 g/ha 剂量下对稗草表现出有前途的芽前除草活性。代表性化合物 6a、6e 和 6i 即使在 40 mg/L 浓度下也没有细胞毒性。理论 DFT 计算表明 HOMO 图谱应被考虑以理解结构-活性关系。本研究为进一步发现新型抗真菌剂或选择性除草剂提供了有用的信息。
