Novel Citral-thiazolyl Hydrazine Derivatives as Promising Antifungal Agents against Phytopathogenic Fungi

Zhang, Li; Shi, Yunfei; Duan, Xinying; He, Wanrong; Si, Hongbin; Wang, Peng; Chen, Shangxing; Luo, Hai; Rao, Xiaoping; Wang, Zongde; Liao, Shengliang

doi:10.1021/acs.jafc.1c04064

Cited by 24 publications

(36 citation statements)

References 36 publications

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“…In contrast, the hyphae of the untreated control group showed a smooth surface and normal growth ( Figure 4 a). Together with previous research findings [ 40 , 41 ], we speculate that the fungal cell walls and cell membranes of T. versicolor are potential targets of the camphor derivatives, but the mechanism of action of camphor derivatives needs further study.…”

Section: Resultssupporting

confidence: 84%

Synthesis, Antifungal Activity, Cytotoxicity and QSAR Study of Camphor Derivatives

Duan

Zhang

et al. 2022

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Control of fungal phytopathogens affecting crops and woodlands is an important goal in environmental management and the maintenance of food security. This work describes the synthesis of 37 camphor derivatives, of which 27 were new compounds. Their antifungal effects on six fungi were evaluated in vitro. Compounds 3a, 4a and 5k showed strong antifungal activity against Trametes versicolor, with EC50 values of 0.43, 6.80 and 4.86 mg/L, respectively, which were better than that of tricyclazole (EC50 118.20 mg/L) and close to or better than that of carbendazim (EC50 1.20 mg/L). The most potent compound, 3a, exhibited broad-spectrum antifungal activity towards six fungi with EC50 values within the range of 0.43–40.18 mg/L. Scanning electron microscopy demonstrated that compounds 3a, 4a and 5k gave irregular growth and shriveling of the mycelia. In vitro cytotoxicity evaluation revealed that the tested camphor derivatives had mild or no cytotoxicity for LO2 and HEK293T cell lines. Quantitative structure−activity relationship (QSAR) analysis revealed that the number of F atoms, relative molecular weight, the atomic orbital electronic population and total charge on the positively charged surfaces of the molecules of camphor derivatives have effects on antifungal activity. The present study may provide a theoretical basis for a high-value use of camphor and could be helpful for the development of novel potential antifungals.

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Section: Resultssupporting

confidence: 84%

Synthesis, Antifungal Activity, Cytotoxicity and QSAR Study of Camphor Derivatives

Duan

Zhang

et al. 2022

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“…This result indicates that fluorine atom substitution of the meta-position could reinforce the antifungal activities of citral-thiourea compounds, which supports findings reported by previous research. 15,36 These results indicate that there exists close contact between the electronic and steric effects of substituent groups and the biological properties of citral-thiourea derivatives. 37,38 In Vivo Antifungal Effects of Derivatives against C. gloeosporioides.…”

Section: ■ Materials and Methodsmentioning

confidence: 76%

“…To this end, botanical fungicides prepared by pinene, camphor, citral, and so on have recently garnered much attention in the field of pesticide research. − Among these, citral, the main component of Litsea cubeba essential oil, is considered the most promising of the fungicides due to having the properties of broad-antifungal activity, low toxicity, and easy modification. − To screen for citral-based derivatives that feature high antifungal activity, current research focus has increasingly shifted toward the synthesis of citral-based derivatives. He et al researched the antifungal effects of synthetic citral-based 1,2,3-triazole compounds against phytopathogenic plant fungi and found that the inhibition rate of these compounds against Colletotrichum orbiculare reached 95.2% at the concentration of 50 mg/L.…”

Section: Introductionmentioning

confidence: 99%

Novel Design of Citral-Thiourea Derivatives for Enhancing Antifungal Potential against Colletotrichum gloeosporioides

Zeng

Zou

Huang

et al. 2023

J. Agric. Food Chem.

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Although much progress has been made in developing botanical fungicides to combat fungal diseases in crops, there remains a great need to improve the efficiency and long-term safety of these fungicides. This study proposes a novel strategy for designing citral-thiourea derivatives that feature such desirable properties. The motivation of the work herein was to enhance the antifungal activity of citral against C. gloeosprioides by exploiting the synergistic effect that arises from combining citral and thiourea compounds, thereby producing citral-thiourea derivatives that exhibit good long-term safety. The results revealed that the generated compounds e1, e3, e6, e18, and g showed remarkable antifungal activities against C. gloeosprioides, with corresponding EC50 values reaching 0.16, 1.66, 1.37, 4.76, and 4.60 mg/L, respectively, showing that the compounds significantly outperformed both the positive control kresoxim-methyl and the commercially available fungicide carbendazim. Furthermore, compound g showed stronger protective efficacy against C. gloeosprioides than carbendazim on mango fruit at 25 mg/L. Investigating the preliminary structure–activity relationship (SAR) of the compounds also revealed that the citral-thiourea derivatives exhibited higher antifungal activities against C. gloeosprioides compared to citral and thiourea compounds. This reinforcement of antifungal activity observed in the derivatives was found to be attributable to the two characteristics of low molecular size and the presence of a fluorine atom in the meta-position of the benzene ring. Beyond this, it was determined from QSAR that two molecular descriptors (the Kier–Hall index (order 3) and Tot dipole of the molecules) were negatively related to the antifungal activity of the citral-thiourea derivatives, while one other (the maximum resonance energy of a C–H bond) was positively related to their antifungal activity. More importantly, the citral-thiourea derivatives with high antifungal activities (i.e., compounds e1, e3, e6, e14, e15, e18, and g) exhibited negligible cytotoxicity to LO2 and HEK293T cell lines. The antifungal mechanism of the generated citral-thiourea derivatives was investigated by scanning electron microscopy (SEM) and relative conductivity. The derivatives were found to affect mycelial morphology and increase fungal cell membrane permeability, thereby resulting in the destruction of fungal cell membranes. These promising results provide novel insights into the study and potential application value of citral-thiourea derivatives as high-efficiency antifungal agents against C. gloeosprioides.

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“…Rice plants with consistent growth at the end of tillering were chosen for the in vivo antifungal activity test. 18 To test the curative effect, activated R. solani was inoculated into the rice and cultivated for 24 h before being sprayed with 6a 5 , 6a 19 , and trifloxystrobin at concentrations of 200, 100, and 50 μg/mL, respectively. Distilled water containing 0.02% Tween 80 was set as a blank control.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…Rice plants with consistent growth at the end of tillering were chosen for the in vivo antifungal activity test . To test the curative effect, activated R.…”

Section: Methodsmentioning

confidence: 99%

Discovery of Terpene-Derived Quaternary Ring Compounds Containing an Oxime Moiety as Potential Fungicides

Pan

et al. 2023

J. Agric. Food Chem.

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Terpene-derived quaternary ring compounds with an oxime moiety were designed and prepared to create fungicides from natural products. A preliminary assessment of their antifungal activity against seven common pathogenic fungi was conducted, and the median effective concentration (EC 50 ) values against Rhizoctonia solani were obtained. The effects of compound 6a 19 (3bromothiophene-containing), which had an outstanding EC 50 value (1.62 μg/mL), on the morphology, ultrastructure, reactive oxygen species production, mitochondrial membrane potential, nuclear morphology, and defense-related and respiration-related enzyme activities of mycelia were evaluated. The test compound was speculated to obstruct the bio-oxidative process, inhibiting mycelial growth. Compound 6a 19 exhibited a satisfactory in vivo control effect on leaf sheath-infected rice plants. After treating rice plants with 50, 100, and 200 μg/mL 6a 19 , the protective and therapeutic efficacy values were 48.3 and 70.3%, 58.6 and 75.7%, and 69.0 and 81.1%, respectively. Moreover, a linear quantitative structure−activity relationship (R 2 = 0.932, F = 61.3, and S 2 = 0.020) was established using density functional theory calculations. Four chemical descriptors that were crucial to the antifungal activity were analyzed: the number of occupied electronic levels of atoms, the minimum atomic orbital electronic population, maximum net atom charge for a H atom, and minimum net atomic charge. In overall consideration of experimental results, it was speculated that the target compounds satisfactorily inhibited R. solani by interfering with biological oxidation pathways, which provided an insight into the future intensive and systematic action mechanism. This research is promising for the invention of novel fungicides from natural terpenes with multiple potential targets and satisfactory ecological compatibility.

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Novel Citral-thiazolyl Hydrazine Derivatives as Promising Antifungal Agents against Phytopathogenic Fungi

Cited by 24 publications

References 36 publications

Synthesis, Antifungal Activity, Cytotoxicity and QSAR Study of Camphor Derivatives

Synthesis, Antifungal Activity, Cytotoxicity and QSAR Study of Camphor Derivatives

Novel Design of Citral-Thiourea Derivatives for Enhancing Antifungal Potential against Colletotrichum gloeosporioides

Discovery of Terpene-Derived Quaternary Ring Compounds Containing an Oxime Moiety as Potential Fungicides

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