Biosynthesis of ergosterol as a relevant molecular target of metal-based antiparasitic and antifungal compounds

Scalese, Gonzalo; Mosquillo, María Florencia; Pérez-Díaz, Leticia; Gambino, Dinorah

doi:10.1016/j.ccr.2023.215608

Cited by 3 publications

References 238 publications

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Design, Synthesis, and Assessment of Fungicidal Activity of Active Substructure 1,2,4-Triazole Containing Coumarin

Lv,

Li,

Lei

et al. 2024

J. Agric. Food Chem.

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Fragment splicing and molecular docking are important techniques in the design of new agrochemicals. Based on our former discovery of 4-(3,4-dichloroisothiazole)-7-hydroxycumarins 1a and 1b as fungicidal leads, following fragment splicing and molecular docking, a series of bioactive substructure 1,2,4-triazole containing coumarins were designed and synthesized. In vitro fungicidal bioassay indicated that compound 7e was more active than 1b against Botrytis cinereal, Cercospora arachidicola, and Sclerotinia sclerotiorum, with a corresponding EC 50 value of 4.02 vs 5.90, 6.03 vs 8.31, and 3.81 vs 5.37 μg/mL, respectively. Compound 7e also showed an EC 50 value of 4.15 μg/mL against Fusarium graminearum. Moreover, compound 7e demonstrated a stronger inhibition than flutriafol against F. graminearum 14-α demethylase, with an IC 50 value of 0.59 and 0.97 μM, respectively. Calculation results based on density functional theory calculation (DFT), molecular dynamics (MD), and molecular mechanics/ Poisson−Boltzmann surface area (MM/PBSA) studies gave a rational explanation between the activity of compound 7e and its structure. This study demonstrates that fragment splicing of 1,2,4-triazole and coumarin is a good technique for discovering a novel fungicide lead.

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