Design, Synthesis, and Action Mechanism of 1,3-Benzodioxole Derivatives as Potent Auxin Receptor Agonists and Root Growth Promoters

Zhikun Yang; Jiahui Xu; Lin Du; Jiaming Yin; Zhao Wang; Fei Yi; Liusheng Duan; Zhaohu Li; Baomin Wang; Kai Shu; Weiming Tan

doi:10.3389/fpls.2022.902902

Design, Synthesis, and Action Mechanism of 1,3-Benzodioxole Derivatives as Potent Auxin Receptor Agonists and Root Growth Promoters

Front Plant Sci. 2022 Jun 10:13:902902. doi: 10.3389/fpls.2022.902902. eCollection 2022.

Authors

Zhikun Yang^{1

2}, Jiahui Xu^{1

3}, Lin Du¹, Jiaming Yin¹, Zhao Wang¹, Fei Yi¹, Liusheng Duan¹, Zhaohu Li¹, Baomin Wang¹, Kai Shu³, Weiming Tan¹

Affiliations

¹ College of Agronomy and Biotechnology, China Agricultural University, Beijing, China.
² College of Pharmaceutical Science & Green Pharmaceutical Collaborative Innovation Center of Yangtze River Del-ta Region, Zhejiang University of Technology, Hangzhou, China.
³ School of Ecology and Environment, Northwestern Polytechnical University, Xi'an, China.

Abstract

Deeper and longer roots allow crops to survive and flourish, but our understanding of the plant growth regulators promoting root system establishment is limited. Here, we report that, a novel auxin receptor agonist, named K-10, had a remarkable promotive effect on root growth in both Arabidopsis thaliana and Oryza sativa through the enhancement of root-related signaling responses. Using computer-aided drug discovery approaches, we developed potent lead compound by screening artificial chemicals on the basis of the auxin receptor TIR1 (Transport Inhibitor Response 1), and a series of N-(benzo[d] [1,3] dioxol-5-yl)-2-(one-benzylthio) acetamides, K-1 to K-22, were designed and synthesized. The results of bioassay showed that K-10 exhibited an excellent root growth-promoting activity far exceeding that of NAA (1-naphthylacetic acid). A further morphological investigation of the auxin related mutants (yucQ, tir1) revealed that K-10 had auxin-like physiological functions and was recognized by TIR1, and K-10 significantly enhanced auxin response reporter's (DR5:GUS) transcriptional activity. Consistently, transcriptome analysis showed that K-10 induced a common transcriptional response with auxin and down-regulated the expression of root growth-inhibiting genes. Further molecular docking analysis revealed that K-10 had a stronger binding ability with TIR1 than NAA. These results indicated that this class of derivatives could be a promising scaffold for the discovery and development of novel auxin receptor agonists, and the employment of K-10 may be effective for enhancing root growth and crop production.

Keywords: 1; 3-benzodioxole derivatives; TIR1; auxin response; root growth regulator; virtual screening.