{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T16:47:29Z","timestamp":1783097249041,"version":"3.54.6"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31471808, 82003941"],"award-info":[{"award-number":["31471808, 82003941"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["ZR2021MC022, ZR2020QC198"],"award-info":[{"award-number":["ZR2021MC022, ZR2020QC198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["663\/1121040"],"award-info":[{"award-number":["663\/1121040"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Shandong Province of China","award":["31471808, 82003941"],"award-info":[{"award-number":["31471808, 82003941"]}]},{"name":"Natural Science Foundation of Shandong Province of China","award":["ZR2021MC022, ZR2020QC198"],"award-info":[{"award-number":["ZR2021MC022, ZR2020QC198"]}]},{"name":"Natural Science Foundation of Shandong Province of China","award":["663\/1121040"],"award-info":[{"award-number":["663\/1121040"]}]},{"name":"Qingdao Agricultural University Doctoral Start-Up Fund","award":["31471808, 82003941"],"award-info":[{"award-number":["31471808, 82003941"]}]},{"name":"Qingdao Agricultural University Doctoral Start-Up Fund","award":["ZR2021MC022, ZR2020QC198"],"award-info":[{"award-number":["ZR2021MC022, ZR2020QC198"]}]},{"name":"Qingdao Agricultural University Doctoral Start-Up Fund","award":["663\/1121040"],"award-info":[{"award-number":["663\/1121040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>(1) Background: Scopoletin and scoparone, two naturally occurring coumarins, have garnered considerable attention and have been introduced to the market in China due to their high insecticidal efficacy and low toxicity. To investigate the structure\u2013activity relationship of these coumarins, a series of scopoletin derivatives with aryl sulfate at C7 and different substitutes at C3 were designed and synthesized, and their insecticidal activity was studied. (2) Methods: A total of 28 new scopoletin derivatives were designed and synthesized. Most target compounds exhibited moderate insecticidal activity against the phytophagous mite Tetranychus cinnabarinus and the brine shrimp Artemia salina. (3) Results: Among these compounds, compounds 5a and 5j possessed the best insecticidal activities against T. cinnabarinus, with LC50 values of 57.0 and 20.0 \u03bcg\/mL, respectively, whereas that of the control drug was 15.0 \u03bcg\/mL. Compound 4j exhibited selective insecticidal activities against A. salina, with an LC50 value of 9.36 \u03bcg\/mL, whereas its LC50 value against T. cinnabarinus was 93.0 \u03bcg\/mL. The enzymatic inhibitory activity on acetylcholinesterase (AChE) showed a consistent tendency with the insecticidal activity. Further molecular docking analyses predicted the binding conformations of these compounds, which showed a good correlation between the insecticidal activity and the binding scores. (4) Conclusions: In general, a decreased electron cloud density of the \u03943,4 olefinic bond is beneficial for improving the insecticidal activity against both T. cinnabarinus and A. salina. In addition, naphthyl or benzene groups with a sulfate ester at the C7 position could further improve the insecticidal activity against A. salina. AChE was implied to be a site of action for potential insecticidal activity. The results provide insight into the rational design of a new generation of effective coumarin insecticides.<\/jats:p>","DOI":"10.3390\/molecules28020530","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T06:11:51Z","timestamp":1672899111000},"page":"530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Design and Synthesis of Scopoletin Sulfonate Derivatives as Potential Insecticidal Agents"],"prefix":"10.3390","volume":"28","author":[{"given":"Congmin","family":"Liu","sequence":"first","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences, Research Center of Bio-Pesticides Engineering & Tech. of Shandong Province, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panyuan","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences, Research Center of Bio-Pesticides Engineering & Tech. of Shandong Province, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences, Research Center of Bio-Pesticides Engineering & Tech. of Shandong Province, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences, Research Center of Bio-Pesticides Engineering & Tech. of Shandong Province, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanping","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences, Research Center of Bio-Pesticides Engineering & Tech. of Shandong Province, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuanghong","family":"Hao","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences, Research Center of Bio-Pesticides Engineering & Tech. of Shandong Province, Qingdao Agricultural University, Qingdao 266109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jeppson, R., Keifer, H.H., and Baker, E.W. (1975). Mites Injurious to Economic Plants, University of California Press.","DOI":"10.1525\/9780520335431"},{"key":"ref_2","unstructured":"Zhang, Q. (2003). Mites of Greenhouses: Identification, Biology and Control, CABI Publishing."},{"key":"ref_3","first-page":"1161","article-title":"On the causes of mite pest outbreaks in mono- and poly-cultured moso bamboo forests","volume":"15","author":"Zhang","year":"2004","journal-title":"J. Appl. Ecol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.biocontrol.2012.09.017","article-title":"Management of spider mite Tetranychus cinnabarinus (Boisduval) (Tetranychidae) infestation in cotton by releasing the predatory mite Neoseiulus pseudolongispinosus (Xin, Liang and Ke) (Phytoseiidae)","volume":"65","author":"Sarwar","year":"2013","journal-title":"Biol. Control"},{"key":"ref_5","first-page":"259","article-title":"Control of the carmine spider mite Tetranychus cinnabarinus boisduval by the predatory mite Phytoseinlus persimilis (Athias-Henriot) in protected strawberries in Aydin, Turkey","volume":"29","author":"Cakmak","year":"2005","journal-title":"Turk. J. Agric. For."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1603\/0022-0493-94.6.1577","article-title":"Cross-resistance, inheritance, and biochemistry of mitochondrial electron transport inhibitor- acaricide resistance in Tetranychus urticae (Acari: Tetranychidae)","volume":"94","author":"Stumpf","year":"2001","journal-title":"J. Econ. Entomol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s12600-013-0309-x","article-title":"Chlorfenapyr resistance in the spider mite Tetranychus urticae: Stability, crossresistance and monitoring of resistance","volume":"41","author":"Nicastro","year":"2013","journal-title":"Phytoparasitica"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/ps.994","article-title":"Acaricide mode of action","volume":"61","author":"Dekeyser","year":"2005","journal-title":"Pest Manag. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10340-012-0442-1","article-title":"Acaricides in modern management of plant-feeding mites","volume":"85","author":"Marcic","year":"2012","journal-title":"J. Pest Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.ibmb.2010.05.008","article-title":"Acaricide resistance mechanisms in the two-spotted spider mite Tetranychus urticae and other important Acari: A review","volume":"40","author":"Vontas","year":"2010","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/1744-7917.12190","article-title":"Resistance status of the carmine spider mite, Tetranychus cinnabarinus and the twospotted spider mite, Tetranychus urticae to selected acaricides on strawberries","volume":"23","author":"Bi","year":"2016","journal-title":"Insect Sci."},{"key":"ref_12","first-page":"3","article-title":"Pesticide resistance of Tetranychus cinnabarinus (Acari: Tetranychidae) in China: A review","volume":"3","author":"Zhang","year":"1998","journal-title":"Syst. Appl. Acarol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1002\/ps.1183","article-title":"Biochemical analysis of a chlorfenapyr-selected resistant strain of Tetranychus urticae Koch","volume":"62","author":"Tirry","year":"2006","journal-title":"Pest Manag. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0031-9422(00)94505-9","article-title":"The induction, by fungal inoculation, of ayapin and scopoletin biosynthesis in Helianthus annuus","volume":"25","author":"Tal","year":"1985","journal-title":"Phytochemistry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1007\/s00299-009-0792-1","article-title":"Streptomyces scabiei and its toxin thaxtomin A induce scopoletin biosynthesis in tobacco and Arabidopsis thaliana","volume":"28","author":"Lerat","year":"2009","journal-title":"Plant Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1744-7917.2010.01350.x","article-title":"Insect feeding deterrent and growth inhibitory activities of scopoletin isolated from Artemisia annua against Spilarctia obliqua (Lepidoptera: Noctuidae)","volume":"18","author":"Tripathi","year":"2011","journal-title":"Insect Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S1671-2927(08)60055-3","article-title":"Studies on acaricidal bioactivities of Artemisia annua L. extracts against Tetranychus cinnabarinus Bois. (Acari: Tetranychidae)","volume":"7","author":"Zhang","year":"2008","journal-title":"Agric. Sci. China"},{"key":"ref_18","first-page":"422","article-title":"Repellent and oviposition deterrent properties of scopoletin to Tetranychus cinnabarinus","volume":"49","author":"Yong","year":"2012","journal-title":"Chin. J. Appl. Entomol."},{"key":"ref_19","first-page":"68","article-title":"Preliminary study on scopoletin toxicity to Tetranychus cinnabarinus and its acaricidal mechanism","volume":"8","author":"Liang","year":"2011","journal-title":"Guangdong Agric. Sci."},{"key":"ref_20","first-page":"826","article-title":"Biochemical evidences for scopoletin inhibits Ca2+-ATPase activity in the carmine spider mite, Tetranychus cinnabarinus (Boisduval)","volume":"4","author":"Hou","year":"2015","journal-title":"Agric. Sci. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.3390\/ijms18071380","article-title":"3d-QSAR and molecular docking studies on the tcpmca1-mediated detoxification of scopoletin and coumarin derivatives","volume":"18","author":"Hou","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Luo, J.X., Lai, T., and Guo, T. (2018). Synthesis and acaricidal activities of scopoletin phenolic ether derivatives: QSAR, molecular docking study and in silico ADME predictions. Molecules, 23.","DOI":"10.3390\/molecules23050995"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bioorg.2015.12.002","article-title":"Synthesis and anti-acetylcholinesterase activity of scopoletin derivatives","volume":"65","author":"Nisachon","year":"2016","journal-title":"Bioorg. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ejmech.2015.01.040","article-title":"Synthesis, in vitro and in vivo antitumor activity of scopoletin-cinnamic acid hybrids","volume":"93","author":"Li","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.14233\/ajchem.2017.20142","article-title":"Green synthesis and characterization of 3-carboxycoumarin and ethylcoumarin -3-carboxylate via Knoevenagel condensation","volume":"29","author":"Syed","year":"2017","journal-title":"Asian J. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5008","DOI":"10.1016\/j.bmcl.2012.06.014","article-title":"Synthesis and in vitro antitumor activity of novel scopoletin derivatives","volume":"22","author":"Liu","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/cbdd.12652","article-title":"Synthesis and biological evaluation of fluorinated 3-phenylcoumarin-7-o-sulfamate derivatives as steroid sulfatase inhibitors","volume":"87","author":"Sebastian","year":"2016","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.3987\/COM-11-12196","article-title":"Synthesis and biological evaluation of a novel series of 1,3-dicoumarinyl-5-aryl-2-pyrazolines","volume":"83","author":"Milanc","year":"2011","journal-title":"Heterocycles"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmech.2014.07.009","article-title":"Design and synthesis of coumarin-3-acylamino derivatives to scavenge radicals and to protect DNA","volume":"84","author":"Yang","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13544","DOI":"10.1021\/acs.jafc.9b05547","article-title":"Design, synthesis, acaricidal activities, and structure-activity relationship studies of novel oxazolines containing sulfonate moieties","volume":"67","author":"Chen","year":"2019","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1584\/jpestics.26.393","article-title":"Synthesis and acaricidal activity of 1-arylmethyl-2-arylimidazolidines","volume":"26","author":"Shinzo","year":"2001","journal-title":"J. Pestic. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1016\/S0278-6915(00)00112-5","article-title":"Toxicity assessment of fumonisins using the brine shrimp (Artemia salina) bioassay","volume":"38","author":"Hartl","year":"2000","journal-title":"Food Chem. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.str.2017.11.021","article-title":"Structure of the G119S Mutant Acetylcholinesterase of the Malaria Vector Anopheles gambiae Reveals Basis of Insecticide Resistance","volume":"26","author":"Cheung","year":"2018","journal-title":"Structure"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/2\/530\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:00:05Z","timestamp":1760119205000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/2\/530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,5]]},"references-count":33,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["molecules28020530"],"URL":"https:\/\/doi.org\/10.3390\/molecules28020530","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,5]]}}}