APAn, a Class of ABA Receptor Agonism/Antagonism Switching Probes.

In plants, biosynthesized ABA undergoes two important physiological processes of signal transduction and metabolism simultaneously. In this study, we described a class of ABA receptor agonist/antagonist switching probes APAn, which can regulate the agonistic activity or antagonistic activity according to the length of a 6'-alkoxyl chain. From APA1 to APA6, with the extension of the alkoxyl chain, it showed a gradually increased receptor-binding potential and decreased HAB1 inhibition activity. Theoretical analysis based on molecular docking and molecular dynamics simulation revealed that some factors outside the ligand-binding pocket in receptors could also affect the binding of the ligand to the receptor, for example, the van der Waals interaction between the alkyl chain in APAn and the 3'-tunnel of ABA receptors made it bind more tightly than iso-PhABA. This enhanced binding made it an antagonist rather than a weakened agonist.

Synthesis and plant growth regulatory activities of 2',3'-PhABA and iso-2',3'-PhABA esters.

Methyl and phenyl esters of 2',3'-PhABA and iso-2',3'-PhABA were prepared for the biological investigation and development of practical applications. These esters exhibited excellent activity in most plant growth inhibitory assays. And, three esters were more efficient than ABA in stomatal closure. The 2',3'-PhABA analogs and their methyl esters have good stability in hydrolysis assay, and the different lipid solubility and permeability of different esters may be one of the origins of their active selectivity for different plants and physiological processes. Furthermore, in the study of drought tolerance, all four esters had comparable activity to ABA. These results suggest that these esters were potent plant growth regulator (PGR) candidates for anti-drought. The finding that different esters have different selective bioactivity and biophysical properties indicates that these esters not only function as ABA-like PGRs but also have the possibility as potential selective pro-hormone. 2',3'-BenzoABA esters as PGR candidates with prolonged and selective bioactivity.

Role of the Ring Methyl Groups in 2',3'-Benzoabscisic Acid Analogues.

Five analogues of iso-PhABA (20) developed earlier by our research group were designed and synthesized. The bioassay results show that the number and position of methyl groups along with the substitution of hydrogen atoms of the methyl group have a great influence on the activity. Compared with iso-PhABA, the inhibitory activity of diMe-PhABA (21) on seed germination and rice seedling growth decreased slightly; however, it significantly reduced the capability of inhibiting wheat embryo germination. Both 3'-deMe- iso-PhABA (22) and 2'-deMe-PhABA (23) exhibited weak inhibitory activities, and 11'-methoxy iso-PhABA (24a/24b) was much more efficient than its isomer 24c/24d in all bioassays. These results reveal the preservation of quaternary carbon at the 2' or 3' position is necessary to maintain its ABA-like biological activity, and demethylation at the 3' position has a more significant effect. The selectivity of these compounds to different physiological processes makes them available as selective probes for different ABA receptors.

Design, synthesis, and insecticidal activity of novel 1-alkoxy-2-nitroguanidines.

In searching for new insecticidal lead compounds, a series of novel 1-alkoxy-2-nitroguanidine, guadipyr analogues bearing alkoxy groups were designed, synthesized and confirmed by 1H NMR, 13C NMR, high-resolution mass spectrometry and X-ray diffraction. The primary bioassays showed that most of these compounds exhibited moderate to good insecticidal activity against Myzus persicae and Aphis gossypii. Especially, the precise insecticidal assay showed that compounds 4-02, 4-07 and 4-08 displayed excellent in vitro activity with IC50 values lower than 10 µg mL-1 to M. persicae which is comparable to guadipyr. On the other hand, the toxicity of compound 4-07 and guadipyr against honey bees was much lower than imidacloprid. The results indicated that the flexible chain on the nitrogen atom was the most crucial factor on honey bee toxicity, which existed in both neonicotinoids and guadipyr series.

Synthesis and Biological Activity of 2',3'-iso-Aryl-abscisic Acid Analogs.

2',3'-iso-Benzoabscisic acid (iso-PhABA), an excellent selective abscisic acid (ABA) analog, was developed in our previous work. In order to find its more structure-activity information, some structural modifications were completed in this paper, including the substitution of phenyl ring and replacing the ring with heterocycles. Thus, 16 novel analogs of iso-PhABA were synthesized and screened with three bioassays, Arabidopsis and lettuce seed germination and rice seedling elongation. Some of them, i.e., 2',3'-iso-pyridoabscisic acid (iso-PyABA) and 2',3'-iso-franoabscisic acid (iso-FrABA), displayed good bioactivities that closed to iso-PhABA and natural (+)-ABA. Some others, for instance, substituted-iso-PhABA, exhibited certain selectivity to different physiological process when compared to iso-PhABA or (+)-ABA. These analogs not only provided new candidates of ABA-like synthetic plant growth regulators (PGRs) for practical application, but also new potential selective agonist/antagonist for probing the specific function of ABA receptors.

Design and Functional Characterization of a Novel Abscisic Acid Analog.

The phytohormone abscisic acid (ABA) plays a crucial role in mediating plant growth and development by recruiting genetically redundant ABA receptors. To overcome its oxidation inactivation, we developed a novel ABA analog named 2',3'-benzo-iso-ABA (iso-PhABA) and studied its function and structural characterization with A. thaliana ABA receptors. The (+)-iso-PhABA form showed much higher ABA-like activities than (+)-ABA including inhibitory effects on the seed germination of lettuce and A. thaliana, wheat embryo germination and rice seedling elongation. The PP2C (protein phosphatases 2C) activity assay showed that (+)-iso-PhABA acted as a potent and selective ABA receptor agonist, which is preferred to PYL10. In some cases, (-)-iso-PhABA showed moderate to high activity for the PYL protein inhibiting PP2C activity, suggesting different mechanisms of action of iso-PhABA and ABA. The complex crystal structure of iso-PhABA with PYL10 was determined and elucidated successfully, revealing that (+)-iso-PhABA was better coordinated in the same binding pocket compared to (+)-ABA. Moreover, the detailed interaction network of iso-PhABA/PYL10 was disclosed and involves hydrogen bonds and multiple hydrophobic interactions that provide a robust framework for the design of novel ABA receptor agonists/antagonists.

Design, synthesis, crystal structure and fungicidal activity of (E)-5-(methoxyimino)-3,5-dihydrobenzo[e][1,2]oxazepin-4(1H)-one analogues.

A practical method of four-step synthesis towards novel (E)-5-(methoxyimino)-3,5-dihydrobenzo[e][1,2]oxazepin-4(1H)-one antifungals is presented, where a commercially available pesticide and pharmacology intermediate, (E)-methyl 2-(2-(bromomethyl)phenyl)-2-(methoxyimino)acetate (1), was used as starting material. These compounds were confirmed by 1H NMR, 13C NMR, high-resolution mass spectroscopy and X-ray crystal structure. Via in vitro fungicidal evaluation, the moderate to high activities of several compounds against eight phytopathogenic fungi were demonstrated. Especially, the fungicidal activities of compounds 5-03 and 5-09 were comparable to those of the controls azoxystrobin and trifloxystrobin in precise virulence measurements for four fungi. These results suggested that dihydrobenzo[e][1,2]oxazepin-4(1H)-one analogues could be considered as potential fungicidal candidates for crop protection.

Correction: Design, synthesis, crystal structure and fungicidal activity of (E)-5-(methoxyimino)-3,5-dihydrobenzo[e][1,2]oxazepin-4(1H)-one analogues.

[This corrects the article DOI: 10.1039/C7MD00025A.].

Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides.

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.