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Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC50 values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 \u03bcg\/mL, respectively, whereas the LC50 value of MA was 659.34 \u03bcg\/mL. Structure\u2013activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 \u03bcg\/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin.<\/jats:p>","DOI":"10.3390\/molecules28073035","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T01:33:00Z","timestamp":1680053580000},"page":"3035","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel Matrine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, and Mechanistic Analysis"],"prefix":"10.3390","volume":"28","author":[{"given":"Song","family":"Ang","sequence":"first","affiliation":[{"name":"School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China"},{"name":"International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfeng","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China"},{"name":"International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wende","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China"},{"name":"International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China"},{"name":"International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxuan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China"},{"name":"International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenping","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China"},{"name":"International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wing-Leung","family":"Wong","sequence":"additional","affiliation":[{"name":"The State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China"},{"name":"International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China"},{"name":"International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6515-0726","authenticated-orcid":false,"given":"Panpan","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China"},{"name":"International Healthcare Innovation Institute (Jiangmen), Jiangmen 529040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111972","DOI":"10.1016\/j.ejmech.2019.111972","article-title":"Quinolizidine alkaloids derivatives from Sophora alopecuroides Linn: Bioactivities, structure-activity relationships and preliminary molecular mechanisms","volume":"188","author":"Li","year":"2020","journal-title":"Eur. 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