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

Abstract

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.

Isolating Antipathogenic Fungal Coumarins from Coriaria nepalensis and Determining Their Primary Mechanism In Vitro

“…The detailed procedure for determining the effect of compound 9 on P. nicotianae mycelia was carried out according to previous methods and recommended in the Supporting Information.…”

“…The effect of compound 9 on P. nicotianae cell apoptosis was studied based on a previously published method . The detailed procedures are described in the Supporting Information.…”

Selective N-functionalization of Arylhydrazines with Primary Alcohols and Acids under PPh3/DDQ System

“…Yellow liquid (35.9 mg, 51% yield); R f = 0.5 (5:1 PE/EA); 1 H NMR (400 MHz, CDCl 3 ) δ 7.36 (t, J = 7.3 Hz, 2H), 7.30 (t, J = 7.3 Hz, 1H), 7.25 (d, J = 8.2 Hz, 2H), 6.59 (dd, J = 10.8, 2.1 Hz, 2H), 6.23−6.16 (m, 1H), 4.59 (s, 2H), 3.59 (brs, 2H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 164.0 (dd, J = 10.5 Hz, J = 161 Hz), 153.7 (d, J = 8.6 Hz), 136.3, 128.9, 127.8, 127.6, 95.9 (dd, J = 4.7 Hz, J = 15.4 Hz), 92.9 (t, J = 17.5 Hz), 59.2; 19 N′-phenylbenzohydrazide (5a). 31 Yellow solid (51.5 mg, 81% yield); mp 171−173 °C; R f = 0.5 (2:1 PE/EA); 1 H NMR (400 MHz, DMSO) δ 10.40 (s, 1H), 7.95 (d, J = 7.7 Hz, 3H), 7.62−7.45 (m, 3H), 7.17 (t, J = 7.2 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 6.73 (t, J = 7.2 Hz, 1H); 13 4-Ethyl-N′-phenylbenzohydrazide (5b). 32 Yellow solid (47.5 mg, 66% yield); mp 135−137 °C; R f = 0.5 (2:1 PE/ EA); 1 H NMR (400 MHz, DMSO) δ 10.30 (s, 1H), 7.86 (d, J = 8.0 Hz, 3H), 7.33 (d, J = 7.9 Hz, 2H), 7.15 (t, J = 7.7 Hz, 2H), 6.79 (d, J = 7.9 Hz, 2H), 6.71 (t, J = 7.2 Hz, 1H), 2.66 (q,…”

“…Yellow solid (44.8 mg, 53% yield); mp 161−163 °C; R f = 0.6 (2:1 PE/EA); 1 H NMR (400 MHz, DMSO) δ 10.32 (s, 1H), 7.90 (s, 1H), 7.88 (d, J = 5.6 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.17 (t, J = 7.8 Hz, 2H), 6.82 (d, J = 7.8 Hz, 2H), 6.73 (t, J = 7.3 Hz, 1H), 2.65 (t, J = 7.6 Hz, 2H), 1.65−1.57 (m, 2H), 1.35−1.26 (m, 4H), 0.88 (t, J = 7.1 Hz, 3H); 13 2-Methyl-N′-phenylbenzohydrazide (5d). 31 Yellow solid (47.5 mg, 70% yield); mp 171−173 °C; R f = 0.5 (2:1 PE/EA); 1 H NMR (400 MHz, DMSO) δ 10.04 (s, 1H), 7.91 (s, 1H), 7.46 (d, J = 6.8 Hz, 1H), 7.37 (t, J = 6.8 Hz, 1H), 7.29 (d, J = 6.4 Hz, 2H), 7.17 (t, J = 7.7 Hz, 2H), 6.82 (d, J = 7.6 Hz, 2H), 6.73 (t, J = 7.2 Hz, 1H), 2.38 (s, 3H); 13 3-Fluoro-N′-phenylbenzohydrazide (5e). 33 Yellow solid (27.6 mg, 40% yield); mp 188−190 °C; R f = 0.7 (2:1 PE/ EA); 1 H NMR (400 MHz, DMSO) δ 10.48 (s, 1H), 7.97 (s, 1H), 7.79 (d, J = 4.8 Hz, 1H), 7.73 (d, J = 6.8 Hz, 1H), 7.57 (q, J = 4.8 Hz, J = 8.8 Hz, 1H), 7.44 (t, J = 6.0 Hz, 1H), 7.17 (t, J = 4.8 Hz, 2H), 6.81 (t, J = 5.6 Hz, 2H), 6.73 (t, J = 4.8 Hz, 1H); 13 3-Bromo-N′-phenylbenzohydrazide (5f).…”

Design, Synthesis, Antibacterial, and Antifungal Evaluation of Phenylthiazole Derivatives Containing a 1,3,4-Thiadiazole Thione Moiety

“…sclerotiorum , a necrotrophic phytopathogenic fungus distributed globally, is capable of causing various symptoms, such as stem rot and pod reduction, leading to annual production losses of 10–50% [ 7 , 8 ]. At present, the application of chemical pesticides is the most effective measure to manage bacterial and fungal diseases of crops [ 9 , 10 ]. However, the misuse and overuse of many conventional pesticides for a long time have created ever-rising resistance, resulting in a significant decrease in the control efficacy of commercial agents [ 11 , 12 ].…”