Strigolactone agonists/antagonists for agricultural applications: New opportunities

Chemical concepts such as isosteres and scaffold hopping have proven to be powerful tools in agrochemical innovation processes. They offer opportunities to modify known molecular lead structures with the aim to improve a range of parameters, including biological efficacy and spectrum, physicochemical properties, stability, and toxicity. While recent biochemical insights into plant-specific receptors and signaling pathways trigger the discovery of the first lead structures, the disclosure of such a new chemical structure sparks a broad range of synthesis activities giving rise to diverse chemical innovation and often a considerable boost in biological activity. Herein, recent examples of isostere concepts in plant-hormone chemistry will be discussed, outlining how synthetic creativity can broaden the scope of natural product chemistry and giving rise to new opportunities in research fields such as abiotic stress tolerance and growth promotion.

Section: Strigolactonesmentioning

confidence: 99%

Inspired by Nature: Isostere Concepts in Plant Hormone Chemistry

Frackenpohl

Abel

Alnafta

et al. 2023

“…Weeds compete with crops for necessary resources, such as nutrients, space, light, and water, causing yield penalties of crops to 34% and more. − Effective weed control methods are essential to sustainable agriculture . Using herbicides has been the most efficient approach to managing weeds .…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Metabolism Studies of N-1,4-Diketophenyltriazinones as Protoporphyrinogen IX Oxidase Inhibitors

Liu

Qin

et al. 2023

Self Cite

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is an established site for green herbicide discovery. In this work, based on structural analysis, we develop an active fragment exchange and link (AFEL) approach to designing a new class of N-1,4-diketophenyltriazinones I–III as potent Nicotiana tabacum PPO (PPO) inhibitors. After systematic structure–activity relationship optimizations, a series of new compounds with K i values in the single-digit nanomolar range toward NtPPO and promising herbicidal activity were discovered. Among them, Ii (K i = 0.11 nM) displays 284- and 90-fold improvement in NtPPO inhibitory activity over trifludimoxazin (K i = 31 nM) and saflufenacil (K i = 10 nM), respectively. In addition, Ip (K i = 2.14 nM) not only exhibited good herbicidal activity at 9.375–37.5 g ai/ha but also showed high crop safety to rice at 75 g ai/ha by the postemergence application, indicating that Ip could be developed as a potential herbicide for weed control in rice fields. Additionally, our molecular dynamic simulation clarified the molecular basis for the interactions of these molecules with NtPPO. The metabolism studies in planta showed that IIIc could be converted to Ic, which displayed higher herbicidal activity than IIIc. The density functional theory analysis showed that due to the effect of two sulfur atoms at the triazinone moiety, IIIc is more reactive than Ic, making it more easily degraded in planta. Our work indicates that the AFEL strategy could be used to design new molecules with improved bioactivity.

“…For these reasons, many artificial SL analogues with simplified structures have been synthesized. Among the artificially synthesized SL mimics, GR24 is the most widely studied compound in plant science, and it has been used as a molecular tool to successfully disentangle the role of phytohormone receptor DWARF14 in SL recognition, as well as to reveal unanticipated mechanisms in SL signaling . As represented by the listed examples in Figure , the lactone structure of the C ring can be replaced by the γ-lactam ring to obtain strigolactam, which is found to increase the germination activity of Orobanche cumana seed by 68% .…”

Section: Introductionmentioning

confidence: 99%

“…19−21 Therefore, discovering and developing novel and effective SL derivatives have always been of great significance in the development of green and ecological agriculture. 22 For the perception and signaling mechanism, SLs specifically bind to the α/β-hydrolase DWARF14 (D14), a non-canonical hormone perception receptor, and the metabolized D-ring intermediate facilitates the interaction of D14 with the F-box protein more axillary growth2 (MAX2). 23 The subsequent signaling requires the involvement of the SKP1-CULLIN-F-BOX (SCF) ubiquitin ligase to form the D14-MAX2-SMAX1-LIKE (SMXL) 6/7/8 complex and trigger the degradation of SMXL6/7/8, thereby releasing the repressed SL-responsive genes and lead to SL-regulated plant responses.…”

Section: ■ Introductionmentioning

confidence: 99%

“…exogenous SLs have a mitigating effect on grape leaves under drought stress and improve drought tolerance . Hypocotyl and root regulation is also a very important application direction of SL phytohormones due to hypocotyl and root development directly affects the photosynthesis and nutrient absorption of plant seedling, which determines the growth and yield of crops. − Therefore, discovering and developing novel and effective SL derivatives have always been of great significance in the development of green and ecological agriculture . For the perception and signaling mechanism, SLs specifically bind to the α/β-hydrolase DWARF14 (D14), a non-canonical hormone perception receptor, and the metabolized D-ring intermediate facilitates the interaction of D14 with the F-box protein more axillary growth2 (MAX2) .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and Biological Profiling of Novel Strigolactone Derivatives for Arabidopsis Growth and Development

Kang,

Yan,

et al. 2023

The artificially synthesized strigolactone (SL) analogue GR24 is currently the most widely used reference compound in studying the biological functions of SLs. To elucidate the structure−activity relationship and find more promising derivatives with unique molecular profiles, we design and synthesized three series of novel GR24 derivatives and explored their activities in hypocotyl and root development of Arabidopsis. Among the 50 synthesized compounds, A11a, A12a, and A20d were found to have high activities comparable to GR24 for hypocotyl and/or primary root elongation inhibition in Arabidopsis. Some new analogues have been discovered to exhibit unique activities: (1) A20c, A21e, and A21o are specific inhibitors in primary root elongation; (2) A21c, A26c, and A27a exhibit a high promotion effect on Arabidopsis primary root elongation; and (3) A27e possesses the most unique profiles completely opposite to GR24 that promotes both hypocotyl elongation and primary root development. Moreover, we revealed that the AtD14 receptor does not affect the inhibitory effect of SL analogues in Arabidopsis root development. The ligand− receptor interactions for the most representative analogues A11a and A27e were deciphered with a long time scale molecular dynamics simulation study, which provides the molecular basis of their distinct functions, and may help scientists design novel phytohormones.