Synthesis and Antiproliferative Evaluation of Novel Longifolene-Derived Tetralone Derivatives Bearing 1,2,4-Triazole Moiety

Zhu, Xia-Ping; Lin, Guo‐Qiang; Duan, Wengui; Li, Qingmin; Li, Fangyao; Lu, Shun-Zhong

doi:10.3390/molecules25040986

Cited by 22 publications

(25 citation statements)

References 29 publications

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“…In continuation of our interest in developing natural product-based bioactive compounds ( Lin et al, 2017 ; Wang X. et al, 2018 ; Lin et al, 2018 ; Kang et al, 2019 ; Liu et al, 2020 ; Zhu et al, 2020 ; Chen et al, 2021 ; He et al, 2021 ), a series of novel nopol derivatives containing 1,2,4-triazole and thioether moieties were designed and synthesized by the strategy of molecular docking-based virtual screening based on the crystal structure of cytochrome bc 1 complex. In addition, a three-dimensional structure-activity quantitative relationship (3D-QSAR) model was established by the comparative molecular field analysis (CoMFA) method.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…The molecular docking study for the target compounds was performed using AutoDock 4.2.6 software 34 according to our previous work. 26 The simulation of the binding pattern for the best antifungal activity of compound 5a and commercial SDHI carboxin with SDH is shown in Figure 3 . The oxygen atoms of carbonyl and phenol moieties interacted with the residues TRP173 and HIS60 via the H bond ( Figure 3 a), which are similar to the commercial SDHI carboxin ( Figure 3 b).…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Antifungal Activity of Novel Longifolene-Derived Diacylhydrazine Compounds

et al. 2021

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Succinate dehydrogenase (SDH) present in the inner mitochondrial membrane is an important target enzyme for the design of SDH inhibitor-type fungicides. Using SDH as the target enzyme, 22 novel longifolene-derived diacylhydrazine compounds were designed and synthesized using the renewable natural product longifolene as the starting material. Their structures were confirmed by IR, 1 H NMR, 13 C NMR, electrospray mass spectrometry, and elemental analysis. In vitro antifungal activity of the target compounds was preliminarily evaluated. As a result, some of them showed better or comparable antifungal activity than that of the commercial fungicide chlorothalonil, in which compound 5a had inhibitory rates of 97.5, 80.5, 72.1, and 67.1% against Physalospora piricola , Colletotrichum orbiculare , Alternaria solani, and Gibberella zeae , respectively, presenting excellent and broad-spectrum activity that deserved further study. Besides, a reasonable and effective three-dimensional structure–activity quantitative relationship model has been established. There was a significant positive correlation between the antifungal activity and the docking-based binding energy analyzed using Spearman’s rank correlation algorithm. Also, the simulative binding pattern of the target compounds with SDH was investigated by molecular docking study. Furthermore, the diacylhydrazine and phenol groups of the target compounds were proposed to be the potential pharmacophores by frontier molecular orbital analysis.

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“…Meanwhile, the properties of molecule such as electrostatic potentials (ESPs) and dipole moments can also affect the bioactivity of compounds. Therefore, the frontier molecular orbitals, ESPs, and dipole moments for compounds 6a (R = Ph), 6h (R = m -Cl Ph), 6i (R = p -Cl Ph), and 6j (R = m, p -Cl Ph) were calculated by means of DFT/B3LYP/6-31G (d, p) in the Gaussian 09 package on the Supercomputing Platform at Guangxi University, and the result was viewed using the GaussView 5 software [ 34 ]. The result is showed in Figure 5 .…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Nopol-Derived 1,3,4-Thiadiazole-Thiourea Compounds

Chen¹,

Duan²,

Lin³

et al. 2021

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A series of novel nopol derivatives bearing the 1,3,4-thiadiazole-thiourea moiety were designed and synthesized by multi-step reactions in search of potent natural product-based antifungal agents. Their structures were confirmed by FT-IR, NMR, ESI-MS, and elemental analysis. Antifungal activity of the target compounds was preliminarily evaluated by in vitro methods against Fusarium oxysporum f. sp. cucumerinum, Cercospora arachidicola, Physalospora piricola, Alternaria solani, Gibberella zeae, Rhizoeotnia solani, Bipolaris maydis, and Colleterichum orbicalare at 50 µg/mL. All the target compounds exhibited better antifungal activity against P. piricola, C. arachidicola, and A. solani. Compound 6j (R = m, p-Cl Ph) showed the best broad-spectrum antifungal activity against all the tested fungi. Compounds 6c (R = m-Me Ph), 6q (R = i-Pr), and 6i (R = p-Cl Ph) had inhibition rates of 86.1%, 86.1%, and 80.2%, respectively, against P. piricola, much better than that of the positive control chlorothalonil. Moreover, compounds 6h (R = m-Cl Ph) and 6n (R = o-CF3 Ph) held inhibition rates of 80.6% and 79.0% against C. arachidicola and G. zeae, respectively, much better than that of the commercial fungicide chlorothalonil. In order to design more effective antifungal compounds against A. solani, analysis of the three-dimensional quantitative structure–activity relationship (3D-QSAR) was carried out using the CoMFA method, and a reasonable and effective 3D-QSAR model (r2 = 0.992, q2 = 0.753) has been established. Furthermore, some intriguing structure–activity relationships were found and are discussed by theoretical calculation.

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Synthesis and Antiproliferative Evaluation of Novel Longifolene-Derived Tetralone Derivatives Bearing 1,2,4-Triazole Moiety

Cited by 22 publications

References 29 publications

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

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

Design, Synthesis, and Antifungal Activity of Novel Longifolene-Derived Diacylhydrazine Compounds

Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Nopol-Derived 1,3,4-Thiadiazole-Thiourea Compounds

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