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This study synthesizes and evaluates cinnamamides derived from cinnamic acid against Aedes aegypti larvae to address rising resistance and toxicity concerns associated with traditional larvicides. Twenty-one analogs were prepared and characterized by NMR and HRMS, and larvicidal assays identified two active compounds, AF03 and AF18, with LC50 values near 42–45 μg/mL. Cytotoxicity was absent in A549 cells, and AF03 showed no zebrafish mortality, with mild irritation only. Enzymatic, morphological, and docking analyses suggested targets including AeSCP-2 and AeKAT, supported by molecular dynamics showing stable interactions and low RMSD, indicating low environmental impact potential.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/new-cinnamamide-and-derivatives-as-new-larvicides-against-aedes-aegypti-vector-larvae-facile-synthesis-in-silico-study-in-vitro-noncytotoxicity-and-nontoxicity-against-zebrafish/443909/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/new-cinnamamide-and-derivatives-as-new-larvicides-against-aedes-aegypti-vector-larvae-facile-synthesis-in-silico-study-in-vitro-noncytotoxicity-and-nontoxicity-against-zebrafish/443909.png","ImageObject",300,407,{"name":42,"@type":43},"Riley West","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-03","2026-09-29",true,{"@type":52,"interactionType":53,"userInteractionCount":26},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"Why are new larvicides needed for Aedes aegypti control?","Question",{"text":62,"@type":63},"Traditional larvicides face challenges including toxicity and increasing resistance in mosquito populations. The study targets safer and more effective alternatives for vector control.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How were the cinnamamide derivatives synthesized and characterized?",{"text":67,"@type":63},"The work synthesized 21 cinnamamides using Steglich coupling or acid chloride formation followed by amidation. The compounds were characterized with 1H NMR, 13C DEPTQ, and HRMS for novel molecules.",{"name":69,"@type":60,"acceptedAnswer":70},"Which compounds showed the strongest larvicidal activity and what were their LC50 values?",{"text":71,"@type":63},"Two compounds were active against fourth-instar A. aegypti larvae: AF03 and AF18. AF03 had LC50 = 41.6 μg/mL and AF18 had LC50 = 45.4 μg/mL.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},443909,1791008230,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":26,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},1099523885074,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","This article is licensed under CC-BY 4.0   \n[http://pubs.acs.org/journal/acsodf](http://pubs.acs.org/journal/acsodf)  Article   \nNew Cinnamamide and Derivatives as New Larvicides against Aedes aegypti Vector Larvae: Facile Synthesis, In Silico Study, In Vitro Noncytotoxicity, and Nontoxicity against Zebrafish  \nPublished as part of ACS Omega special issue “Chemistry in Brazil: Advancing through Open Science”. Adrielle Firmino da Silva, Saraliny Bezerra Frana, Erick Gabriel Alves Ferreira,  \nEmiliano de Oliveira Barreto, Jeniffer Mclaine Duarte de Freitas, Johnnatan Duarte de Freitas, Edeildo Ferreira da Silva J́unior, Ana Catarina Rezende Leite, Pedro Correia Gomes dos Santos, Rafael David Souto de Azevedo, Josefa Gerlane da Silva, and Dimas José da Paz Lima*  \n Cite This: ACS Omega 2025, 10, 59078−59095  \nRead Online  \n\n|  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- |\n| ACCESS   | Metrics & More |  |  Article Recommendations |  | *sı Supporting Information |\n\nABSTRACT: Every year, millions of people are infected by arboviruses, such as Dengue, a neglected disease that mainly affects regions with lower socioeconomic development. One of the main strategies to combat these diseases is population control of mosquito vectors, such as Aedes aegypti. Chemical control is an effective approach to reducing the population of these vectors; however, challenges such as toxicity and increasing resistance in populations make it necessary to search for new bioactive and selective substances continuously. In this sense, this study presents the synthesis and evaluation of the larvicidal activity of cinnamamides derived from cinnamic acid against the larvae of the A. aegypti mosquito. Given the increase in resistance to traditional larvicides, this research aims to offer safer and more effective alternatives for vector control. In this study, we synthesized 21 cinnamamides featuring scaffolds with and without electron-withdrawing substituents as well as variations in the amide side chain with aliphatic and aromatic groups (the latter containing a −CH2− spacer). The compounds were obtained via Steglich coupling or acid chloride formation followed by amidation and characterized by 1H NMR, 13C DEPTQ, and HRMS (for novel molecules). Larvicidal assays against fourth-instar A. aegypti revealed two active compounds: (E)-N-allyl-3-(4-chlorophenyl)acrylamide (AF03, LC50 = 41.6 μg/mL) and (E)-N-allyl-3-(4-(trifluoromethoxy)phenyl)acrylamide (AF18, LC50 = 45.4 μg/mL). Cytotoxicity tests indicated that both molecules were nontoxic to A549 cells (5−100 μg/mL). AF03 was further evaluated in chicken erythrocytes, showing no effect on oxygen transport, and in zebrafish, where it caused mild irritation but no mortality. Enzymatic assays showed that AF03 increased acetylcholinesterase (AChE) activity in the zebrafish brain, slightly elevated catalase (CAT) activity in the liver and heart (similar to solvent effects), and increased superoxide dismutase (SOD) activity in the brain but not in the heart. Morphological analysis suggested potential involvement of receptor, transport, or digestive proteins as biological targets. Molecular docking identified sterol carrier protein-2 (AeSCP-2, PDB: 2ksi) and kynurenine aminotransferase (AeKAT, PDB: 1yiy) as promising targets, with AeSCP-2 selected for molecular dynamics simulations. MD results confirmed a stable and specific interaction between AF03 and AeSCP-2, supported by the global structural stability of the protein and the low RMSD values of the ligand. This study suggests that cinnamamides may lead to the development of new, effective larvicidal agents with a low environmental impact.  \n1. INTRODUCTION  \nDiseases caused by arboviruses represent a major global public health challenge with a wide geographical distribution, particularly in tropical regions. This is largely due to highly efficient vectors such as the Aedes aegypti mosquito, which is responsible for the transmission of emerging and re-emerging","cbCaifzlYk8cmFH7","https://ap.wps.com/l/cbCaifzlYk8cmFH7","pdf",11259551,18,"English","# Abstract\n# Introduction\n# Materials and Methods\n## Synthesis and Characterization\n## Larvicidal Assays\n## Cytotoxicity and Zebrafish Evaluation\n## Enzymatic Assays\n## Molecular Docking and Dynamics","[{\"question\":\"Why are new larvicides needed for Aedes aegypti control?\",\"answer\":\"Traditional larvicides face challenges including toxicity and increasing resistance in mosquito populations. The study targets safer and more effective alternatives for vector control.\"},{\"question\":\"How were the cinnamamide derivatives synthesized and characterized?\",\"answer\":\"The work synthesized 21 cinnamamides using Steglich coupling or acid chloride formation followed by amidation. The compounds were characterized with 1H NMR, 13C DEPTQ, and HRMS for novel molecules.\"},{\"question\":\"Which compounds showed the strongest larvicidal activity and what were their LC50 values?\",\"answer\":\"Two compounds were active against fourth-instar A. aegypti larvae: AF03 and AF18. AF03 had LC50 = 41.6 μg/mL and AF18 had LC50 = 45.4 μg/mL.\"}]","New Cinnamamide and Derivatives as New Larvicides against Aedes aegypti Vector Larvae - Facile Synthesis - In Silico Study - In Vitro Noncytotoxicity - and Nontoxicity against Zebrafish | PDF",1790706013,45]