CHEMISTRY & BIODIVERSITY
·
2023
·Vol. 20
·期 8
·e202300958
·
IF 2.9
Bo Luo,Chongchong Zhang,Suya Liang,Wei Zhou,Yihan Hu,Yulin Li,Jiayi Hu,Lailiang Qu
In search for SDHIs fungicides, twenty-five novel carboxamides containing a chalcone scaffold were designed, synthesized, and evaluated for antifungal activities against five pathogenic fungi. The results showed that compound 5 k exhibited outstanding antifungal activity against R. solani with an EC 50 value of 0.20 μg/mL, which was much better than that of commercial SDHIs Boscalid (EC 50 =0.74 μg/mL). Moreover, compound 5 k also displayed promising antifungal activities against S. sclerotiorum , B. cinerea , and A. alternate (IC 50 =2.53–4.06 μg/mL), indicating that 5 k had broad-spectrum antifungal activity. Additionally, in vivo antifungal activities results showed that 5 k could significantly inhibit the growth of R. solani in rice leaves with good protective efficacy (57.78 %) and curative efficacy (58.45 %) at 100 μg/mL, both of which were much better than those of Boscalid, indicating a promising application prospect. Moreover, SEM analysis showed that compound 5 k could remarkably disrupt the typical structure and morphology of R. solani hyphae. Further SDH enzyme inhibition assay and molecular docking study revealed that lead compound 5 k had a similar mechanism of action as commercial SDHI Boscalid. These results indicated that compound 5 k showed potential as a SDHIs fungicide and deserved further investigation. Graphical
研究领域:
农药化学
·
植物保护
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
MYCOPATHOLOGIA
·
2025
·Vol. 190
·期 5
·1-16
·
IF 2.9
Zhang Heng,Zhu Zhangling,Peng Mengqi,Liu Sijie,Gong Xiao,Chen Tian,Hu Qingwen,Li Linyun,Dun-zhu Zha-xi,Drol-ga Lha-zom,Sun Yi
Introduction Aspergillus fumigatus poses significant clinical challenges due to its increasing azole resistance. This study investigates the sdh1 gene's role in regulating azole susceptibility, mitochondrial function, and virulence. Materials and Methods Fungal strains were co-cultured with varying concentrations of succinate dehydrogenase inhibitors (SDHIs). Post-treatment azole minimum inhibitory concentrations (MICs) were determined using broth microdilution method, while succinate dehydrogenase subunit (SDH) expression changes were analyzed via RT-qPCR. Using A. fumigatus MFIG001 as the parental strain, sdh1 knockout mutant (Δ sdh1 ) and complemented strain (Δ sdh1::sdh1 + ) were constructed through homologous recombination. Detect the hyphal growth rate of Δ sdh1 , MICs and the changes in virulence within the Galleria mellonella infection model. Mitochondrial function was evaluated by measuring SDH activity, ATP content, and reactive oxygen species (ROS) levels. Transcriptomic changes were analyzed using RNA-seq and RT-qPCR, with efflux pump activity validated through Rhodamine 6G accumulation assays. Results Exposure to subinhibitory concentrations of SDHIs induced azole resistance in A. fumigatus , with 4.12% of strains exhibiting reduced susceptibility to voriconazole, itraconazole, and posaconazole. RT-qPCR analysis revealed significant downregulation of sdh1 in resistant strains, implicating its role in resistance development. Deletion of sdh1 resulted in an 8- to 16-fold increase in triazole MICs, confirming its role as a negative regulator of azole susceptibility. Phenotypically, the Δ sdh1 strain exhibited impaired growth, reduced sporulation, and diminished efficacy of azole treatment in the G. mellonella infection model. Furthermore, Δ sdh1 exhibited severe mitochondrial dysfunction, including reduced SDH activity, decreased ATP levels, elevated ROS, and impaired antioxidant defenses. RNA-seq analysis revealed that the deletion of sdh1 upregulated the expression of efflux pump genes (e.g., cdr1B , abcB , mdr4 ), while Rhodamine 6G efflux assays demonstrated significantly enhanced efflux activity. Discussion These results identify sdh1 as a critical determinant of azole susceptibility through dual mechanisms: mitochondrial function maintenance and efflux pump regulation. The observed SDHI-induced cross-resistance suggests agricultural fungicides may drive environmental selection of azole-resistant strains. While sdh1 deletion increased drug tolerance through efflux activation, the concurrent mitochondrial damage reduced pathogenic fitness, revealing compensatory evolutionary constraints. This work highlights the need to monitor non-target effects of agricultural SDHIs on clinical antifungal resistance.
研究领域:
医学真菌学
·
抗真菌耐药
·
分子微生物学
·
环境与健康
·
线粒体生物学
·
药物相互作用
·
感染性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2023
·
IF 3.8
Bo Luo,Wei Zhou,Xingai Zhang,Pei Zhao,Xiaoxiao Zhang,Longge Zhang,Hongyan Ding,Lailiang Qu
To promote the discovery and development of novel SDHIs fungicides, a series of novel pyrazole-4-carboxamides 4a-t and aromatic carboxamides 8a-i with a hydrazine scaffold were designed, synthesized, and evaluated for their antifungal activities. The results showed that compound 4i exhibited outstanding antifungal activity against R. solani with EC 50 value of 0.24 μg/mL, which was about three times more potent than that of Boscalid (EC 50 = 0.74 μg/mL). Moreover, compound 4i also displayed promising antifungal activities against Sclerotinia sclerotiorum, B. cinerea, Alternaria alternate , and F. graminearum (IC 50 = 1.21–4.50 μg/mL), indicating a broad spectrum of antifungal activities. Additionally, in vivo antifungal activities results showed that 4i could significantly inhibit the growth of R. solani in rice leaves with good protective efficacy (55.21%) and excellent curative efficacy (73.06%) at 100 μg/mL. The results of the SDH enzymatic inhibition assay showed that compound 4i generated significant SDH inhibition with IC 50 value of 6.47 μM, which was superior to Boscalid (IC 50 = 7.92 μM). Furthermore, SEM analysis showed that compound 4i could remarkably disrupt the typical structure and morphology of R. solani hyphae. The molecular docking study revealed that compound 4i could form H-bonds interactions and π-π interactions with TRP173 and TRY58 at the activity site of SDH, which was similar to that of Boscalid. The DFT calculation provided crucial information regarding electron transfer, which was essential in understanding the mechanism of molecules and target enzymes. These results indicated that compound 4i showed potential as a SDHIs fungicide and warranted further investigation.
研究领域:
植物保护
·
药物化学
·
真菌学
✓ 已验证
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Bo Luo,Yuerui Wu,Xinran Ren,Huimin Li,Xuanru Li,Gege Wang,Mengjia Wang,Luqi Dong,Mengxing Liu,Wei Zhou,Lailiang Qu
In the search for novel succinate dehydrogenase inhibitor (SDHI) fungicides to control Rhizoctonia solani, thirty-five novel pyrazole-4-carboxamides bearing either an oxime ether or an oxime ester group were designed and prepared based on the strategy of molecular hybridization, and their antifungal activities against five plant pathogenic fungi were also investigated. The results indicated that the majority of the compounds containing oxime ether demonstrated outstanding in vitro antifungal activity against R. solani, and some compounds also displayed pronounced antifungal activities against Sclerotinia sclerotiorum and Botrytis cinerea. Particularly, compound 5e exhibited the most promising antifungal activity against R. solani with an EC50 value of 0.039 μg/mL, which was about 20-fold better than that of boscalid (EC50 = 0.799 μg/mL) and 4-fold more potent than fluxapyroxad (EC50 = 0.131 μg/mL). Moreover, the results of the detached leaf assay showed that compound 5e could suppress the growth of R. solani in rice leaves with significant protective efficacies (86.8%) at 100 μg/mL, superior to boscalid (68.1%) and fluxapyroxad (80.6%), indicating promising application prospects. In addition, the succinate dehydrogenase (SDH) enzymatic inhibition assay revealed that compound 5e generated remarkable SDH inhibition (IC50 = 2.04 μM), which was obviously more potent than those of boscalid (IC50 = 7.92 μM) and fluxapyroxad (IC50 = 6.15 μM). Furthermore, SEM analysis showed that compound 5e caused a remarkable disruption to the characteristic structure and morphology of R. solani hyphae, resulting in significant damage. The molecular docking analysis demonstrated that compound 5e could fit into the identical binding pocket of SDH through hydrogen bond interactions as well as fluxapyroxad, indicating that they had a similar antifungal mechanism. The density functional theory and electrostatic potential calculations provided useful information regarding electron distribution and electron transfer, which contributed to understanding the structural features and antifungal mechanism of the lead compound. These findings suggested that compound 5e could be a promising candidate for SDHI fungicides to control R. solani, warranting further investigation.
研究领域:
植物病理学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·Vol. 74
·期 33
·25976-25989
·
IF 6.7
Luo Bo,Hu Yihan,Zhao Yi,Tao Yuchen,Feng Xiaoyu,Li Dan,Wang Yinge,Hu Xinyue,Wu Yanbing
As part of an ongoing effort to develop novel succinate
dehydrogenase
inhibitors (SDHIs), a range of innovative nicotinamide derivatives
featuring stilbene scaffolds were synthesized and assessed for their
antifungal properties. Lead compounds 6g and 6c demonstrated significant antifungal efficacies against Rhizoctonia solani and Sclerotinia sclerotiorum , with EC 50 (half maximal effective
concentration) values of 0.008 and 0.034 μg/mL, respectively,
surpassing Boscalid (EC 50 = 0.573 and 0.455 μg/mL,
respectively) and Fluxapyroxad (EC 50 = 0.026 and 0.037
μg/mL, respectively). Detached leaf assays further confirmed
their excellent protective and curative effects, outperforming Boscalid
and Fluxapyroxad. Further studies revealed that compound 6g operated through a mechanism akin to Boscalid and Fluxapyroxad.
These results indicated that both 6g and 6c showed great potential as novel SDHIs for effectively managing R. solani and S. sclerotiorum , underscoring the necessity for further research to fully explore
their capabilities.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·Vol. 74
·期 33
·26031-26042
·
IF 6.7
Luo Bo,Wu Yanbing,Zhang Qingsi,Liu Xinyi,Cui Huanxi,Gao Zhanghan,Niu Wenjing,Zhao Xiaoyang,Li Dan,Feng Xiaoyu,Hu Yihan,Chai Jianqi,Fang Kun,Zhu Dongyang
In this study, 30 tetrahydroquinoline-based pyrazole-4-carboxamide
derivatives were designed, synthesized, and screened for antifungal
activities. Among them, compound 6m displayed the strongest
inhibitory activity against Rhizoctonia solani , with a half-maximal effective concentration (EC 50 ) as
low as 0.03 μg/mL, superior to Boscalid (EC 50 = 0.40
μg/mL) and Fluxapyroxad (EC 50 = 0.06 μg/mL).
Further detached-leaf assays on rice verified that 6m could markedly suppress the growth of R. solani with strong protective and curative effects even at 50 μg/mL.
Follow-up mechanistic studies indicated that compound 6m might exert antifungal activity through SDH inhibition-related mechanisms.
These findings suggested that compound 6m might be a
potent candidate as a succinate dehydrogenase inhibitor (SDHI) against R. solani . Further research, including field trials
and biosafety assessment, was needed to realize the potential of compound 6m as an effective tool for rice protection.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Bo Luo,Yanbing Wu,Mengfan Cao,Chendan Liu,Heran Xiong,Yuqing Guo,Miao Wang,Lu Yu,Ruxin Han,Mengxing Liu
In the ongoing search for more potent succinate dehydrogenase inhibitors (SDHIs) for agricultural applications, 30 pyrazole-4-carboxamide derivatives bearing a thioether group were designed and synthesized via bioisosteric replacement and scaffold-hopping based on the structure of two SDHIs lead compounds in our previous work. The antifungal efficacy of these target compounds was evaluated against five major plant pathogenic fungi, and the results indicated that the majority of the synthesized compounds exhibited strong antifungal activities, particularly against Rhizoctonia solani and Sclerotinia sclerotiorum. Among these, compound 8e emerged as the most promising candidate, displaying exceptional antifungal potency against R. solani (EC50 = 0.012 μg/mL) and S. sclerotiorum (EC50 = 0.123 μg/mL), significantly superior to boscalid (EC50 = 0.464 μg/mL and 0.159 μg/mL, respectively) and comparable to fluxapyroxad (EC50 = 0.036 μg/mL and 0.104 μg/mL). Additionally, detached leaf assays revealed that compound 8e effectively inhibited the growth of R. solani on rice leaves and S. sclerotiorum on oilseed rape leaves, achieving significant protective efficacies of 89.1% and 93.9%, respectively, at 100 μg/mL, which were superior to boscalid (68.8% and 90.5%) and comparable to fluxapyroxad (86.4% and 98.6%), indicating a promising potential for crop protection in the field, particularly for rice and oilseed rape. Furthermore, SDH enzymatic inhibition assays showed that compound 8e exhibited potent SDH inhibition (IC50 = 1.30 μM), which was more effective than boscalid (IC50 = 1.53 μM) and close to fluxapyroxad (IC50 = 0.35 μM), confirming its role as an effective SDHI. SEM analysis showed that compound 8e caused significant structural disruption and morphological damage to the hyphae of R. solani, further supporting its antifungal activity. The results of molecular docking and DFT and ESP calculations demonstrated that compound 8e had a similar antifungal mechanism to fluxapyroxad. These findings suggested that compound 8e held great promise as a potential SDHI candidate for protection of crops such as rice and oilseed rape, warranting further investigation.
研究领域:
农业化学
·
药物化学
·
植物病理学
·
生物化学
·
农药科学
·
计算生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Bo Luo,Mengxing Liu,Rongrong Li,Mengnan Zhou,Fengjia Zhang,Miao Wang,Yuqing Guo,Qingsi Zhang,Xinyi Liu,Yanbing Wu,Kun Fang,Rong Wang
In the search for novel succinate dehydrogenase inhibitors (SDHIs) fungicides for managing rice sheath blight (RSB) and sclerotinia stem rot (SSR), 28 pyrazole-4-carboxamides incorporating stilbene or diphenylacetylene scaffolds were synthesized and evaluated for antifungal activities. The results showed that compound 7m exhibited the most promising antifungal efficacy against Rhizoctonia solani and Sclerotinia sclerotiorum with EC50 (half maximal effective concentration) values of 0.004 and 0.028 μg/mL, outperforming Boscalid and Fluxapyroxad. Furthermore, the detached leaf assay showed that 7m showed remarkable protective and curative efficacies against R. solani and significant inhibition of S. sclerotiorum growth on oilseed rape leaves, indicating that it had a promising application prospect for RSB and SSR management. Further SDH enzymatic inhibition assay, scanning electron microscopy (SEM), molecular docking studies, and molecular dynamics (MD) simulations revealed that compound 7m shared an antifungal mechanism similar to that of Fluxapyroxad, which was further validated by density functional theory (DFT) and electrostatic potential (ESP) calculations. These findings suggested that 7m held significant promise as a novel SDHI for the effective management of RSB and SSR, warranting further investigation.
研究领域:
农业化学
·
植物病理学
·
杀菌剂开发
·
计算化学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR DIVERSITY
·
2024
·
IF 3.9
Zhang Yuhao,Zhou Bohang,Wei Pengan,Liu Le,Bai Ruofei,Wang Yiwei,Zhou Le
Succinate dehydrogenase inhibitors (SDHIs) as one of the fastest-growing fungicide categories for plant protection. In this study, a series of N ′-phenyl pyridylcarbohydrazides as analogues of commercial SDHIs were designed and evaluated for inhibition activity on phytopathogenic fungi to search for potential novel SDHIs. The determination of antifungal activity in vitro and in vivo led to the discovery of a series of compounds with high activity and broad-spectrum property. Especially, N ′-(4-fluorophenyl)picolinohydrazide ( 1c ) and N ′-(3,4-fluorophenyl)picolinohydrazide ( 1ae ) showed 0.041–1.851 μg/mL of EC 50 values on twelve fungi, superior to positive controls carbendazim and boscalid. In vivo activity, 1c at 50 μg/mL showed 61% of control efficacy at the post-treatment 9th day for the infection of P. piricola on apples, slightly smaller than 70% of carbendazim. In terms of action mechanism, 1c showed strong inhibition activity with IC 50 of 0.107 μg/mL on SDH in Alternaria brassicae , superior to positive SDHI boscalid (IC 50 0.182 μg/mL). Molecular docking indicated that 1c can well bind with the ubiquinone-binding region of SDH mainly by hydrogen bond, carbon hydrogen bond, π-alkyl, amide- π stacking, F–N and F–H interactions. Furthermore, scanning and transmission electron micrographs showed that 1c was able to obviously change the structure of mycelia and cell membrane. Fluorescence staining analysis showed that 1c could increase both the intracellular reactive oxygen species level and mitochondrial membrane potential. Finally, seed germination test, seedling growth test and cytotoxicity assay showed that 1c had very low toxicity to plant growth and mammalian cells. Thus, N ′-phenyl pyridylcarbohydrazides especially 1c and 1ae can be considered promising fungicide alternatives for plant protection. Graphical abstract
研究领域:
植物保护
·
植物病理学
·
分子生物学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2023
·Vol. 79
·期 5
·1922-1930
·
IF 4.1
Zhi Ma,Shuo Qiu,Dong Zhang,Xinying Guo,Yuele Lu,Yongxian Fan,Xiaolong Chen
BACKGROUND Succinate dehydrogenase inhibitor (SDHI) fungicides are an important class of agricultural fungicides with the advantages of high efficiency and a broad bactericidal spectrum. To pursue novel SDHIs, a series of N -substituted dithiin tetracarboximide derivatives were designed, synthesized, and characterized by 1 H NMR, 13 C NMR, and high resolution mass spectrum (HRMS). RESULTS These engineered compounds displayed potent fungicidal activity against phytopathogens, including Sclerotinia sclerotiorum , Botrytis cinerea , and Rhizoctonia solani , comparable with that of the commercial SDHI fungicide boscalid . In particular, compound 18 stood out with prominent activity against S. sclerotiorum with a half-maximal effective concentration (EC 50 ) value of 1.37 μg ml −1 . Compound 1 exhibited the most potent antifungal activity against B. cinerea with EC 50 values of 5.02 μg ml −1 . As for R. solani , 12 and 13 exhibited remarkably inhibitory activity with EC 50 values of 4.26 and 5.76 μg ml −1 , respectively. In the succinate dehydrogenase (SDH) inhibition assay, 13 presented significant inhibitory activity with a half-maximal inhibitory concentration (IC 50 ) value of 15.3 μ m , which was approximately equivalent to that of boscalid (14.2 μ m ). Furthermore, molecular docking studies revealed that 13 could anchor in the binding site of SDH. CONCLUSION Taken together, results suggested that the dithiin tetracarboximide scaffold possessed a huge potential to be developed as novel fungicides and SDHIs. © 2023 Society of Chemical Industry.
研究领域:
农业化学
·
药物化学
·
植物病理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）