Abstract
A series of novel menthol derivatives containing 1,2,4-triazole-thioether moiety were designed, synthesized, characterized structurally, and evaluated biologically to explore more potent natural product-based antifungal agents. The bioassay results revealed that at 50 μg/mL, some of the target compounds exhibited good inhibitory activity against the tested fungi, especially against Physalospora piricola. Compounds 5b (R = o-CH3 Ph), 5i (R = o-Cl Ph), 5v (R = m,p-OCH3 Ph) and 5x (R = α-furyl) had inhibition rates of 93.3%, 79.4%, and 79.4%, respectively, against P. piricola, much better than that of the positive control chlorothalonil. Compounds 5v (R = m,p-OCH3 Ph) and 5g (R = o-Cl Ph) held inhibition rates of 82.4% and 86.5% against Cercospora arachidicola and Gibberella zeae, respectively, much better than that of the commercial fungicide chlorothalonil. Compound 5b (R = o-CH3 Ph) displayed antifungal activity of 90.5% and 83.8%, respectively, against Colleterichum orbicalare and Fusarium oxysporum f. sp. cucumerinum. Compounds 5m (R = o-I Ph) had inhibition rates of 88.6%, 80.0%, and 88.0%, respectively, against F. oxysporum f. sp. cucumerinu, Bipolaris maydis and C. orbiculare. Furthermore, compound 5b (R = o-CH3 Ph) showed the best and broad-spectrum antifungal activity against all the tested fungi. To design more effective antifungal compounds against P. piricola, 3D-QSAR analysis was performed using the CoMFA method, and a reasonable 3D-QSAR model (r2 = 0.991, q2 = 0.514) was established. The simulative binding pattern of the target compounds with cytochrome P450 14α-sterol demethylase (CYP51) was investigated by molecular docking.
Highlights
Fungicides have been widely used for controlling the disease caused by plant pathogens.the developed resistance of plant-pathogenic fungi to currently commercial fungicides has shown great threat to the production and quality of plants, which lead to the exploration of novel antifungal agents.Peppermint (Mentha Canadensis Linnaeus) is an important herb spice plant mainly planted in Jiangsu and Anhui regions of China, as well as a traditional Chinese medicine.Menthol, (1R, 2S, 5R)-2- isopropyl-5-methylcyclohexan-1-ol, is the dominant constituent of the essential oil which is obtained by steam distillation of the fresh leaves of peppermint [1].The content of menthol in peppermint essential oil can be as high as 30% to 55% [2]
The developed resistance of plant-pathogenic fungi to currently commercial fungicides has shown great threat to the production and quality of plants, which lead to the exploration of novel antifungal agents
Their structures were confirmed by triazole-thioether compounds were synthesized
Summary
Menthol, (1R, 2S, 5R)-2- isopropyl-5-methylcyclohexan-1-ol, is the dominant constituent of the essential oil which is obtained by steam distillation of the fresh leaves of peppermint [1]. The content of menthol in peppermint essential oil can be as high as 30% to 55% [2]. Menthol and its derivatives have a wide range of applications in medicine and agrochemical, such as anti-inflammatory [3], antimicrobial [4,5], antifungal [6], insecticidal [7], anticancer [8,9], analgesic [10,11], anesthetic [12] and penetration-enhancing activities [13]. Menthol deserves further study for agrochemical or pharmaceutical use based on its bioactive property and chemical reactivity
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