Synthesis of 3‐carene‐derived nanocellulose/1,3,4‐thiadiazole‐amide complexes with antifungal activity for plant protection

Abstract

BACKGROUND Nanopesticides have been proved to be a powerful and promising tool to solve the issues in agriculture. The purpose of the present study was to develop ecofriendly nanopesticide systems by the strategy of comprehensive utilization of two natural biomass resources (bagasse and turpentine oil) because of their incomparable advantages. RESULTS In this research, a series of nanocellulose carriers ETOCN‐1–ETOCN‐4 (ETOCN, esterified TEMPO‐oxidized cellulose nanofibers) with different degrees of substitution were prepared and characterized by Fourier‐transform infrared (FTIR), X‐ray diffraction (XRD) and transmission electron microscopy (TEM). Then, 21 1,3,4‐thiadiazole‐amide compounds 8a–8u containing gem‐dimethylcyclopropane ring were designed, synthesized and characterized. A preliminary bioassay indicated that compound 8i (R = p‐Br Ph) exhibited broad‐spectrum antifungal activity against the tested fungi. Furthermore, drug‐loading complexes 8i/ETOCN‐1–8i/ETOCN‐4 were fabricated by integration of nanocellulose‐based carriers ETOCN‐1–ETOCN‐4 with bioactive compound 8i, and the drug‐loading capacities, microstructures and sustained‐releasing performance of these complexes were also investigated. According to the observation of scanning electron microscopy (SEM) images of complex 8i/ETOCN‐2, the small‐molecule drug and the carrier formed a well‐distributed and compact complex, which led to the excellent drug‐loading capacity and sustained‐releasing performance in the ethanol/water (1:1, v/v) system. CONCLUSIONS Complexes 8i/ETOCN‐1–8i/ETOCN‐4 deserved further study as the promising candidates for the development of nanopesticides. © 2022 Society of Chemical Industry.

Synthesis, antifungal activity, and DFT calculation study of novel 1-acyl-5- amino-1,2,4-triazole-thioether derivatives containing natural gem-dimethylcyclopropane ring structure

“…A series of 1-acyl-5-amino-1,2,4-triazole-thioether derivatives containing natural gem-dimethylcyclopropane ring structure 7a -7r were synthesized according to Scheme 1. Intermediates 1, 2, 3, and 4 were prepared by our previously reported methods [24] using renewable biomass resource 3-carene as starting material. Intermediates 6a -6r were prepared by nucleophilic substitution of 3-amino-5-mercapto-1,2,4-triazole with a series of alkyl halides.…”

“…The intermediates 1, 2, 3, and 4 were prepared by the method reported in our previous work. [24] Then, a solution of intermediate 4 (0.2g, 1.1 mmol) dissolved in dry DCM (10 mL) was slowly added to a mixed solution of the intermediate 5 (1.0 mmol) and Et 3 N in dry DCM (20 mL) under an anhydrous atmosphere and with ice bath cooling. After the reaction was completed, some saturated aqueous NaHCO 3 was added to quench the unreacted intermediate 4.…”

“…[21] For example, thioether-containing fenamidone is a powerful fungicide used in potato elds to control potato late blight (Phytophthora infestans). [22] In light of the aforementioned clues and our previous works on the exploration of natural product-derived bioactive compounds, [23][24][25][26] a series of novel 1-acyl-5-amino-1,2,4-triazole-thioether derivatives containing natural gem-dimethylcyclopropane ring structure were designed and synthesized by the fusion of gemdimethylcyclopropane ring and 1,2,4-triazole-thioether moiety. Their structures were con rmed by FT-IR, NMR, ESI-MS, and elemental analysis.…”

Synthesis, Antifungal Activity, and Molecular Docking Study of Novel 3‐Carene‐Derived 4‐Substituted Phenyl‐1,2,4‐Triazolinthiones Bearing gem‐Dimethylcyclopropane Moiety

“…[14] To our surprise, it could serve as a natural source of cyclopropane ring, which was proved to be an important building block for bioactive compounds. [15][16][17] Especially, cyclopropane ring has been found in several commercial antifungal agents, [18] such as Prothioconazole, Cyproconazole, Isoflucypram and Sedaxane (Figure 1).…”

“…Furthermore, 1,2,4-triazolinthione compounds retained the essential skeleton of 1,2,4-triazole ring, and the introduction of C=S and NÀ H would be more beneficial to the formation of hydrogen bonds between bioactive small-molecules and biological targets. Based on the above-mentioned clues and our previous works [15,16,[27][28][29][30] on natural product-derived bioactive compounds, a series of novel 3-carene-derived 4-substituted phenyl-1,2,4-triazolinthiones bearing gem-dimethylcyclopropane moiety were synthesized and structurally characterized by UV/VIS, FT-IR, 1 H-NMR, 13 C-NMR, ESI-MS and elemental analysis. The in vitro antifungal activities of all the target compounds were preliminarily tested, and the binding modes of the target compound with high activity and CYP51 were also investigated by molecular docking.…”