Structural fine-tuning analogues of quinabactin revealed the differences of their binding microenvironment with ABA receptors and their influence on plant phenotypes

Abstract

Abstract Quinabactin (QB, 3) is an important ABA functional analogue without ABA-like structure and has great application potential in agriculture. In order to address the key factors affecting the binding mode of quinabactin to ABA receptors and plant phenotypes, several QB analogues with fine-tuned lactam ring and sulfonamide group were designed and synthesized. Their effects on plant phenotypes, such as seed germination, seedling growth, stomatal movement and drought tolerance, were screened. Meanwhile, their binding affinity to ABA receptors, inhibitory activities on HAB1 phosphatase and ABA-response gene regulation abilities were evaluated. The results showed that their affinities to ABA receptors displayed subtle differences and were highly consistent with their influence on plant phenotypes. DHQB increased the inhibitory activity of QB on rice leaf growth by nearly one fold, showed that the weak activity of QB on monocots could be improved by its structure optimization. The change of sulfonamide orientation had the greatest influence on receptor binding and apparent bioactivities, whereas the poor activity of TFTQB (25) reflected the binding boundary between these analogues and ABA receptors. The change of a single factor on lactam ring had little effect on all activities, although activities were all slightly decreased. These effects were obviously due to the differences in their binding to ABA receptors, which had been reasonably explained by the molecular docking model. This study provided constructive insights for the development of novel quinabactin analogues.