Sheng-Xin Sun

Bio: Sheng-Xin Sun is an academic researcher from Nanjing Agricultural University. The author has contributed to research in topics: Medicine & Chemistry. The author has an hindex of 1, co-authored 2 publications receiving 3 citations.

Design, synthesis, antifungal evaluation, and molecular docking of novel 1,2,4-triazole derivatives containing oxime ether and cyclopropyl moieties as potential sterol demethylase inhibitors

Abstract: In the search for novel sterol demethylase inhibitors (DMIs), a series of 1,2,4-triazole derivatives containing oxime ether and cyclopropyl moieties were designed using the bioactive substructure combination assisted by virtual molecular docking. The above-mentioned target compounds were characterized using the 1H NMR, 13C NMR, 19F NMR, and HR-MS spectra. The antifungal evaluation against Rhizoctonia solani (Rs), Fusarium graminearum (Fg), and Botrytis cinerea (Bc) indicated that most of the target compounds exhibited remarkable inhibitory activities against the above-mentioned tested fungi. Significantly, the compound 5k exhibited outstanding anti-Fg activity with an EC50 value of 1.22 μg mL−1in vitro, and a protective effect of 59.45% in vivo at 200 μg mL−1. Further investigation revealed that compound 5k evidently inhibited Fg spore germination and caused some wrinkles and dents on the surface of mycelia. Molecular docking showed that compound 5k bound with the target protein FgCYP51 via coordination, hydrogen bonding and stacking interactions that were similar, but slightly different from the interactions of tebuconazole with FgCYP51. These research results suggested that the target compounds are valuable for the further structural optimization of novel triazole fungicides.

Practical Synthesis and Antifungal Investigation of Drimane Meroterpenoids Enabled by Nickel-Catalyzed Decarboxylative Coupling.

Abstract: Drimane meroterpenoids have drawn increasing attention in the discovery of novel pharmaceutical leads owing to their structural diversity and bioactivity variation, but further development is significantly impeded by the lack of an efficient modular route of preparation. A nickel-catalyzed decarboxylative cross-coupling paradigm has been established to expeditiously access a constellation of drimane meroterpenoids. The redox-active drimane precursor is a bench-stable coupling partner and is easily available from the inexpensive feedstock sclareol. This transformation features the tolerance of challenging functional groups (phenol, aldehyde, ester, etc.) and mild conditions with a low-cost nickel catalytic system. The synthetic utility is further highlighted by the direct scalable synthesis of challenging drimane meroterpenoids as diversifiable advanced intermediates for late-stage functionalizations. This method facilitated antifungal investigations and culminated in the discovery of compounds C8 and C3 as new antifungal leads against Rhizoctonia solani, with EC50 values of 4.9 and 7.2 μM, respectively.

Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates.

Abstract: The discovery of novel and easily available leads provides a convincing solution to agrochemical innovation. A bioassay-guided scaffold subtraction of the previous "Chem-Bio Model" isoquinoline-3-oxazoline MIQOX was conducted for identifying the easily available isoquinoline-3-hydrazide as a novel antifungal scaffold. The special and practical potential of this model was demonstrated by a phenotypic antifungal bioassay, molecular docking, and cross-resistance evaluation. A panel of antifungal leads (LW2, LW3, and LW11) was acquired, showing much better antifungal performance than the positive controls. Specifically, compound LW3 exhibited a broad antifungal spectrum holding EC50 values as low as 0.54, 0.09, 1.52, and 2.65 mg/L against B. cinerea, R. solani, S. sclerotiorum , and F. graminearum, respectively. It demonstrated a curative efficacy better than that of boscalid in controlling the plant disease caused by B. cinerea. The candidate LW3 did not show cross-resistance to the extensively used succinate dehydrogenase inhibitor (SDHI) fungicides and can efficiently inhibit resistant B. cinerea strains. The molecular docking of compound LW3 is quite different from that of the positive controls boscalid and fluopyram. This progress highlights the practicality of isoquinoline hydrazide as a novel model in fungicide innovation.

Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors.

Abstract: Up to now, a total of 24 succinate dehydrogenase inhibitors (SDHIs) fungicides have been commercialized, and SDHIs fungicides were also one of the most active fungicides developed in recent years. Carboxamide derivatives represented an important class of SDHIs with broad spectrum of antifungal activities. In this review, the development of carboxamide derivatives as SDHIs with great significances were summarized. In addition, the structure-activity relationships (SARs) of antifungal activities of carboxamide derivatives as SDHIs was also summarized based on the analysis of the structures of the commercial SDHIs and lead compounds. Moreover, the cause of resistance of SDHIs and some solutions were also introduced. Finally, the development trend of SDHIs fungicides was prospected. We hope this review will give a guide for the development of novel SDHIs fungicides in the future.

Novel Pyrazole-4-acetohydrazide Derivatives Potentially Targeting Fungal Succinate Dehydrogenase: Design, Synthesis, Three-Dimensional Quantitative Structure-Activity Relationship, and Molecular Docking.

Abstract: Succinate dehydrogenase inhibitors (SDHIs) have emerged in fungicide markets as one of the fastest-growing categories that are widely applied in agricultural production for crop protection. Currently, the structural modification focusing on the flexible amide link of SDHI molecules is being gradually identified as one of the innovative strategies for developing novel highly efficient and broad-spectrum fungicides. Based on the above structural features, a series of pyrazole-4-acetohydrazide derivatives potentially targeting fungal SDH were constructed and evaluated for their antifungal effects against Rhizoctonia solani, Fusarium graminearum, and Botrytis cinerea. Strikingly, the in vitro EC50 values of constructed pyrazole-4-acetohydrazides 6w against R. solani, 6c against F. graminearum, and 6f against B. cinerea were, respectively, determined as 0.27, 1.94, and 1.93 μg/mL, which were obviously superior to that of boscalid against R. solani (0.94 μg/mL), fluopyram against F. graminearum (9.37 μg/mL), and B. cinerea (1.94 μg/mL). Concurrently, the effects of the substituent steric, electrostatic, hydrophobic, and hydrogen-bond fields on structure-activity relationships were elaborated by the reliable comparative molecular field analysis and comparative molecular similarity index analysis models. Subsequently, the practical value of pyrazole-4-acetohydrazide derivative 6w as a potential SDHI was ascertained by the relative surveys on the in vivo anti-R. solani preventative efficacy, inhibitory effects against fungal SDH, and molecular docking studies. The present results provide an indispensable complement for the structural optimization of antifungal leads potentially targeting SDH.

Synthesis, 3D-QSAR and Molecular Docking Study of Nopol-Based 1,2,4-Triazole-Thioether Compounds as Potential Antifungal Agents.

Abstract: Cytochrome bc 1 complex is an important component of cellular respiratory chain, and it is also an important target enzyme to inhibit the growth of plant pathogens. Using cytochrome bc 1 complex as the target enzyme, twenty-three novel nopol-based 1,2,4-triazole-thioether compounds were designed and synthesized from natural preponderant resource β-pinene, and their structures were confirmed by FT-IR, NMR, ESI-MS and elemental analysis. The in vitro antifungal activity of the target compounds 5a-5w was preliminarily evaluated against eight plant pathogens at the concentration of 50 µg/ml. The bioassay results showed that the target compounds exhibited the best antifungal activity against Physalospora piricola, in which compounds 5b (R= o-CH3 Ph), 5e (R= o-OCH3 Ph), 5h (R= o-F Ph), 5m (R= o-Br Ph), 5o (R= m,m-OCH3 Ph), and 5r (R= p-OH Ph) had inhibition rates of 91.4, 83.3, 86.7, 83.8, 91.4 and 87.3%, respectively, much better than that of the positive control chlorothalonil. Also, compound 5a (R= Ph) had inhibition rate of 87.9% against Rhizoeotnia solani, and compound 5b (R= o-CH3 Ph) had inhibition rates of 87.6 and 89% against Bipolaris maydis and Colleterichum orbicala, respectively. In order to develop novel and promising antifungal compounds against P. piricola, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method on the basis of their antifungal activity data, and a reasonable and effective 3D-QSAR model (r 2 = 0.944, q 2 = 0.685) has been established. In addition, the theoretical study of molecular docking revealed that the target compounds could bind to and interact with the site of cytochrome bc 1 complex.