Laboratory bioassay, greenhouse experiment and 3D‐QSAR studies on berberine analogues: a search for new herbicides based on natural products

Abstract BACKGROUND Berberine is a herbicidal chemical that we isolated from Coptis chinensis . In continuation of our program aimed at discovering and developing natural botanical herbicides, we evaluated the herbicidal activities of 39 berberine analogues and developed a three‐dimensional quantitative structure–activity relationship (3D‐QSAR) model. RESULTS Among these 39 analogs, the most active compounds were determined to be worenine chloride and coptisine chloride, with median inhibitory concentration (IC 50 ) values on all eight tested weed species of < 10 mg L −1 . As a reference, the IC 50 values of berberine on six weed species were < 10 mg L −1 . Furthermore, the results of a greenhouse experiment showed that at 10 mg L −1 , and 7 days after treatment, the effects of worenine chloride and coptisine chloride on Lemna minor and Ageratum conyzoides were significantly higher than those of glyphosate and sulcotrione. In the 3D‐QSAR analysis, the electrostatic field contour map indicated that introducing an electropositive group in the N‐7, C‐9 and C‐10 positions would potentially improve the inhibition rate. A positively charged nitrogen atom at the N‐7 position was important for activity. Replacement of ‐OCH 3 by ‐OH at the C‐9 and C‐10 positions could decrease the inhibitory activity, while the hydrophobic field contour map revealed that the hydrophobicity of the C‐10 position was associated with high activity. Moreover, the hydrogen bond acceptor field contour map suggested that the existence of a hydrogen bond acceptor at the C‐3 and C‐9 positions might affect the inhibition rate. CONCLUSIONS 3D‐QSAR provided meaningful clues to the structural features of berberine analogues that will assist the design of more potent herbicidal compounds in the future. © 2020 Society of Chemical Industry