Synthesis, 3D-QSAR and Molecular Docking Study of Nopol-Based 1,2,4-Triazole-Thioether Compounds as Potential Antifungal Agents

Abstract

Cytochrome bc1 complex is an important component of cellular respiratory chain, and it is also an important target enzyme to inhibit the growth of plant pathogens. Using cytochrome bc1 complex as the target enzyme, twenty-three novel nopol-based 1,2,4-triazole-thioether compounds were designed and synthesized from natural preponderant resource β-pinene, and their structures were confirmed by FT-IR, NMR, ESI-MS and elemental analysis. The in vitro antifungal activity of the target compounds 5a-5w was preliminarily evaluated against eight plant pathogens at the concentration of 50 µg/ml. The bioassay results showed that the target compounds exhibited the best antifungal activity against Physalospora piricola, in which compounds 5b (R= o-CH3 Ph), 5e (R= o-OCH3 Ph), 5h (R= o-F Ph), 5m (R= o-Br Ph), 5o (R= m,m-OCH3 Ph), and 5r (R= p-OH Ph) had inhibition rates of 91.4, 83.3, 86.7, 83.8, 91.4 and 87.3%, respectively, much better than that of the positive control chlorothalonil. Also, compound 5a (R= Ph) had inhibition rate of 87.9% against Rhizoeotnia solani, and compound 5b (R= o-CH3 Ph) had inhibition rates of 87.6 and 89% against Bipolaris maydis and Colleterichum orbicala, respectively. In order to develop novel and promising antifungal compounds against P. piricola, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method on the basis of their antifungal activity data, and a reasonable and effective 3D-QSAR model (r2 = 0.944, q2 = 0.685) has been established. In addition, the theoretical study of molecular docking revealed that the target compounds could bind to and interact with the site of cytochrome bc1 complex.

Synthesis, Characterization, DFT Mechanistic Study, Antimicrobial Activity, Molecular Modeling, and ADMET Properties of Novel Pyrazole-isoxazoline Hybrids

“…The observed difference in inhibitory activity between the various 6a – m hybrid compounds investigated may be related to the effect and nature of the substituents of the phenyl rings (Ar and Ar 1 ) of the pyrazole and isoxazoline cores. This is consistent with reported works in the literature that demonstrate how electron-donating and electron-withdrawing substituents like nitro, chlorine, bromine, methyl, and methoxy groups affect biological activity. − As the obtained results indicate, some compounds with specific substituents turned out to be more active. Among the examined hybrids, compound 6d (Ar = p -Cl­(C 6 H 4 ), Ar 1 = p -Cl­(C 6 H 4 ) displays the best antibacterial activity against S.…”

Synthesis of Benzimidazole-1,2,4-triazole Derivatives as Potential Antifungal Agents Targeting 14α-Demethylase

“…Carbendazole, benomyl, and thiabendazole have been frequently used among them. − Triazoles, a type of heterocyclic molecule, are favored scaffolds in a variety of fields. Fluconazole, itraconazole, and voriconazole are antifungal medicines available for therapeutic use that contain 1,2,4-triazole fragments. − In recent years, many studies have been conducted on the antifungal activities of triazoles. − Antifungal drugs with benzimidazole and triazole structures and the chemical structure of the designed compounds are shown in Figure .…”

Synthesis and Antitumor Evaluation of Menthone-Derived Pyrimidine-Urea Compounds as Potential PI3K/Akt/mTOR Signaling Pathway Inhibitor

“…In addition, it is an effective strategy in drug development to integrate various pharmacophores to obtain novel molecules with synergistic effect. In continuation of our interest in natural product-based antitumor compounds ( Li et al, 2017 ; Wang et al, 2018 ; Chen Y. et al, 2020 ; Li et al, 2020 ; Zhu et al, 2020 ; Wang et al, 2021 ), a series of novel menthone-derived compounds containing pyrimidine and urea moieties were designed and synthesized according to the strategy, which was shown in Figure 1 . The in vitro antitumor activities of the menthone derivatives against the four tumor cell lines were evaluated.…”