Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions
Thirty phenolic ether derivatives of scopoletin modified at the 7-hydroxy position were synthesized, and their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and elemental analysis. Preliminary acaricidal activities of these compounds against female adults of Tetranychus cinnabarinus (Boisduva...
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| Format: | Article |
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MDPI AG
2018-04-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/5/995 |
| _version_ | 1818128367317155840 |
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| author | Jinxiang Luo Ting Lai Tao Guo Fei Chen Linli Zhang Wei Ding Yongqiang Zhang |
| author_facet | Jinxiang Luo Ting Lai Tao Guo Fei Chen Linli Zhang Wei Ding Yongqiang Zhang |
| author_sort | Jinxiang Luo |
| collection | DOAJ |
| description | Thirty phenolic ether derivatives of scopoletin modified at the 7-hydroxy position were synthesized, and their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and elemental analysis. Preliminary acaricidal activities of these compounds against female adults of Tetranychus cinnabarinus (Boisduval) were evaluated using the slide-dip method. The results indicated that some of these compounds exhibit more pronounced acaricidal activity than scopoletin, especially compounds 32, 20, 28, 27 and 8 which exhibited about 8.41-, 7.32-, 7.23-, 6.76-, and 6.65-fold higher acaricidal potency. Compound 32 possessed the the most promising acaricidal activity and exhibited about 1.45-fold higher acaricidal potency against T. cinnabarinus than propargite. Statistically significant 2D-QSAR model supports the observed acaricidal activities and reveals that polarizability (HATS5p) was the most important parameter controlling bioactivity. 3D-QSAR (CoMFA: q2 = 0.802, r2 = 0.993; CoMSIA: q2 = 0.735, r2 = 0.965) results show that bulky substituents at R4, R1, R2 and R5 (C6, C3, C4, and C7) positions, electron positive groups at R5 (C7) position, hydrophobic groups at R1 (C3) and R2 (C4), H-bond donors groups at R1 (C3) and R4 (C6) will increase their acaricidal activity, which provide a good insight into the molecular features relevant to the acaricidal activity for further designing novel acaricidal agents. Molecular docking demonstrates that these selected derivatives display different bide modes with TcPMCA1 from lead compound and they interact with more key amino acid residues than scopoletin. In silico ADME properties of scopoletin and its phenolic ether derivatives were also analyzed and showed potential to develop as good acaricidal candidates. |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T07:32:07Z |
| publishDate | 2018-04-01 |
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| series | Molecules |
| spelling | doaj.art-653c92c7783643b5975dac9e43c759b62022-12-22T01:15:47ZengMDPI AGMolecules1420-30492018-04-0123599510.3390/molecules23050995molecules23050995Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME PredictionsJinxiang Luo0Ting Lai1Tao Guo2Fei Chen3Linli Zhang4Wei Ding5Yongqiang Zhang6College of Plant Protection, Southwest University, Chongqing 400715, ChinaCollege of Plant Protection, Southwest University, Chongqing 400715, ChinaCollege of Plant Protection, Southwest University, Chongqing 400715, ChinaCollege of Plant Protection, Southwest University, Chongqing 400715, ChinaCollege of Plant Protection, Southwest University, Chongqing 400715, ChinaCollege of Plant Protection, Southwest University, Chongqing 400715, ChinaCollege of Plant Protection, Southwest University, Chongqing 400715, ChinaThirty phenolic ether derivatives of scopoletin modified at the 7-hydroxy position were synthesized, and their structures were confirmed by IR, 1H-NMR, 13C-NMR, MS and elemental analysis. Preliminary acaricidal activities of these compounds against female adults of Tetranychus cinnabarinus (Boisduval) were evaluated using the slide-dip method. The results indicated that some of these compounds exhibit more pronounced acaricidal activity than scopoletin, especially compounds 32, 20, 28, 27 and 8 which exhibited about 8.41-, 7.32-, 7.23-, 6.76-, and 6.65-fold higher acaricidal potency. Compound 32 possessed the the most promising acaricidal activity and exhibited about 1.45-fold higher acaricidal potency against T. cinnabarinus than propargite. Statistically significant 2D-QSAR model supports the observed acaricidal activities and reveals that polarizability (HATS5p) was the most important parameter controlling bioactivity. 3D-QSAR (CoMFA: q2 = 0.802, r2 = 0.993; CoMSIA: q2 = 0.735, r2 = 0.965) results show that bulky substituents at R4, R1, R2 and R5 (C6, C3, C4, and C7) positions, electron positive groups at R5 (C7) position, hydrophobic groups at R1 (C3) and R2 (C4), H-bond donors groups at R1 (C3) and R4 (C6) will increase their acaricidal activity, which provide a good insight into the molecular features relevant to the acaricidal activity for further designing novel acaricidal agents. Molecular docking demonstrates that these selected derivatives display different bide modes with TcPMCA1 from lead compound and they interact with more key amino acid residues than scopoletin. In silico ADME properties of scopoletin and its phenolic ether derivatives were also analyzed and showed potential to develop as good acaricidal candidates.http://www.mdpi.com/1420-3049/23/5/995scopoletinacaricidal activityQSARmolecular dockingADME properties |
| spellingShingle | Jinxiang Luo Ting Lai Tao Guo Fei Chen Linli Zhang Wei Ding Yongqiang Zhang Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions Molecules scopoletin acaricidal activity QSAR molecular docking ADME properties |
| title | Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions |
| title_full | Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions |
| title_fullStr | Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions |
| title_full_unstemmed | Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions |
| title_short | Synthesis and Acaricidal Activities of Scopoletin Phenolic Ether Derivatives: QSAR, Molecular Docking Study and in Silico ADME Predictions |
| title_sort | synthesis and acaricidal activities of scopoletin phenolic ether derivatives qsar molecular docking study and in silico adme predictions |
| topic | scopoletin acaricidal activity QSAR molecular docking ADME properties |
| url | http://www.mdpi.com/1420-3049/23/5/995 |
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