New 7-Chloro-9-methyl-2-phenyl-3,4-dihydro-β-carbolin-2-iums as Promising Fungicide Candidates: Design, Synthesis, and Bioactivity

Yang

et al. 2023

Self Cite

Based on the structural features of both succinate dehydrogenase inhibitors (SDHIs) and targeted covalent inhibitors, a series of N-phenylpropiolamides containing a Michael acceptor moiety were designed to find new antifungal compounds. Nineteen compounds showed potent inhibition activity in vitro on nine species of plant pathogenic fungi. Compounds 9 and 13 showed higher activity on most of the fungi than the standard drug azoxystrobin. Compound 13 could completely inhibit Physalospora piricola infection on apples at 200 μg/mL concentration over 7 days and showed high safety to seed germination and seedling growth of plants at ≤100 μg/mL concentration. The action mechanism showed that 13 is an SDH inhibitor with a median inhibitory concentration, IC 50 , value of 0.55 μg/mL, comparable with that of the positive drug boscalid. Molecular docking studies revealed that 13 can bind well to the ubiquinone-binding region of SDH by hydrogen bonds and undergoes π−alkyl interaction and π−cation interaction. At the cellular level, 1 as the parent compound could destruct the mycelial structure of P. piricola and partly dissolve the cell wall and/or membrane. Structure−activity relationship analysis showed that the acetenyl group should be a structure determinant for the activity, and the substitution pattern of the phenyl ring can significantly impact the activity. Thus, Nphenylpropiolamide emerged as a novel and promising lead scaffold for the development of new SDHIs for plant protection.

Section: Methodsmentioning

confidence: 99%

Discovery of N-Phenylpropiolamide as a Novel Succinate Dehydrogenase Inhibitor Scaffold with Broad-Spectrum Antifungal Activity on Phytopathogenic Fungi

Yang

et al. 2023

Self Cite

“…The safety evaluation of parent compound 2c was carried out by the seed germination method. 49 The mature seeds of Vigna unguiculate (Shenzhou No. 8) were selected as the test material.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…Those infected tomatoes were kept in a 28 °C and 70% humidity incubator for 7–8 days. Every treatment was replicated three times …”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis, Structure–Activity Relationship, and Mechanism of a Series of Diarylhydrazide Compounds as Potential Antifungal Agents

Liu

et al. 2023

A series of simple diarylhydrazide derivatives (45 examples) were well-designed, prepared, and screened for their antifungal activities both in vitro and in vivo. Bioassay results suggested that all designed compounds had significant activity against Alternaria brassicae (EC 50 = 0.30−8.35 μg/mL). Among of them, 2c, as the highest activity compound, could effectively inhibit the growth of plant pathogens Pyricularia oryza, Fusarium solani, Alternaria solani, Alternaria brassicae, and Alternaria alternate and was more potent than carbendazim and thiabendazole. 2c showed almost 100% protection at 200 μg/mL in vivo activity against A. solani in tomato. Moreover, 2c did not affect the germination of cowpea seed and the growth of normal human hepatocytes. The preliminary mechanistic exploration documented that 2c could result in the abnormal morphology and irregular structure of the cell membrane, destroy the function of mitochondria, increase the reactive oxygen species, and inhibit the proliferation of hypha cell. The above results manifested that target compound 2c could be a potential fungicidal candidate against phytopathogenic diseases for its excellent fungicidal activities.

“…After cooling, a fresh fungus cake (5.00 mm in diameter) was inoculated at the center of the culture dishes, and the above-mentioned culture dishes were placed in a constant-temperature incubator (25 °C, dark condition). After the diameter of fungal colonies reached 5.00 cm, the square mycelial dish (5.00 mm in length) situated at the edge of fungal colonies was collected, frozen by liquid nitrogen, and observed by a Hitachi SU8010 scanning electron microscope to acquire the SEM images showing mycelial morphologies. , The hyphae collected from the edge of fungal colonies were fixed with glutaraldehyde (2.50%) and osmic acid (2.00%), dehydrated by acetone, cut into thin slices, and observed by a Hitachi H-600 transmission electron microscope to acquire the morphological images showing mycelial ultrastructures. , …”

Section: Materials and Methodsmentioning

confidence: 99%

Expedient Discovery for Novel Antifungal Leads Inhibiting Fusarium graminearum: 3-(Phenylamino)quinazolin-4(3H)-ones Deriving from Systematic Optimizations on a Tryptanthrin Structure

Wang¹,

Chai

Gu³

et al. 2022

The ever-increasing resistance of Fusarium graminearum has emerged as a pressing agricultural issue that could be settled by developing novel fungicides owning inimitable action mechanisms. With the aim of discovering novel antifungal leads inhibiting F. graminearum, a tryptanthrin structure was dexterously optimized to generate 30 novel quinazolin-4(3H)-one derivatives. The aforementioned optimization generated the molecule C 17 that owned exhilarating in vitro anti-F. graminearum effect (EC50 value = 0.76 μg/mL). Whereafter, the in vivo anti-F. graminearum preventative efficacy of the molecule C 17 was measured to be 59.5% at 200 μg/mL, which was approximately comparable with that of carbendazim (64.9%). Furthermore, morphological observations indicated that the molecule C 17 could cause the hypha to become slender and dense, distort the outline of cell walls, induce an increase in liposome numbers, and cause the reduction of mitochondria numbers. The above results have emerged as an obbligato complement for developing novel antifungal leads that could effectively control Fusarium head blight.