cycloxaprid
{{Chembox
| Verifiedfields = changed
| verifiedrevid = 477223302
| Name = Cycloxaprid
| ImageFile = Cycloxaprid.svg
| ImageSize = 250
| IUPACName = (1S,8R)-5-[(6-chloropyridin-3-yl)methyl]-7-nitro-11-oxa-2,5-diazatricyclo[6.2.1.02,6]undec-6-ene
| OtherNames = {{ubl|Cycloxaprid|(5S,8R)-1-[(6-chloro-3-pyridinyl)methyl]-2,3,5,6,7,8-hexahydro-9-nitro-5,8-Epoxy-1H-imidazo[1,2-a]azepine}}
| Section1 = {{Chembox Identifiers
| CASNo = 1203791-41-6
| PubChem = 45278274
| ChemSpiderID = 31123584
| UNII =
| ChEMBL = 2227757
| StdInChI=1S/C14H15ClN4O3/c15-11-3-1-9(7-16-11)8-17-5-6-18-12-4-2-10(22-12)13(14(17)18)19(20)21/h1,3,7,10,12H,2,4-6,8H2/t10-,12+/m1/s1
| StdInChIKey = NDHXMRFNYMNBKO-PWSUYJOCSA-N
| SMILES = C1C[C@H]2N3CCN(C3=C([C@@H]1O2)[N+](=O)[O-])CC4=CN=C(C=C4)Cl
| QID = Q125351047
}}
| Section2 = {{Chembox Properties
| C=14 | H=15 | Cl=1 | N=4 | O=3
}}
| Section3 = {{Chembox Hazards
| GHSPictograms = {{GHS07}} {{GHS08}} {{GHS09}}
| GHSSignalWord = Warning
| HPhrases = {{HPhrases|H302|H312|H315|H319|H332|H351|H410}}
| PPhrases = {{PPhrases|P273|P280|P301+P312|P305+P351+P338|P501}}
}}
}}
Cycloxaprid is a neonicotinoid insecticide derived from the (nitromethylene)imidazole (NMI) analogue of imidacloprid. First reported in 2008.,{{Cite journal |last1=Shao |first1=Xusheng |last2=Zhang |first2=Wenwen |last3=Peng |first3=Yanqing |last4=Li |first4=Zhong |last5=Tian |first5=Zhongzhen |last6=Qian |first6=Xuhong |date=2008-12-15 |title=cis-Nitromethylene neonicotinoids as new nicotinic family: Synthesis, structural diversity, and insecticidal evaluation of hexahydroimidazo[1,2-α]pyridine |url=https://linkinghub.elsevier.com/retrieve/pii/S0960894X08012341 |journal=Bioorganic & Medicinal Chemistry Letters |volume=18 |issue=24 |pages=6513–6516 |doi=10.1016/j.bmcl.2008.10.048 |pmid=18951786 |issn=0960-894X|url-access=subscription }} it is a novel insecticide developed to control pests that have developed resistance to imidacloprid, particularly targeting lepidopteran pests and whiteflies in rice cultivation. Currently, limited information is available regarding its environmental impact, ecotoxicology, or effects on human health.{{Cite web |last=Hertfordshire |first=University of |title=Cycloxaprid |url=https://sitem.herts.ac.uk/aeru/ppdb/en/Reports/3291.htm |access-date=2024-11-09 |website=sitem.herts.ac.uk}}
Chemistry
Cycloxaprid is distinguished by its unique chemical structure, featuring a nitro substituent in the cis-configuration, unlike other commercialized neonicotinoids which have the nitro group in the trans-configuration. It has demonstrated significant efficacy against insecticide-resistant pests, particularly showing 50-fold higher activity against imidacloprid-resistant brown planthopper compared to imidacloprid itself. This enhanced effectiveness against resistant pests makes it a promising alternative in pest management strategies, especially in contexts where repeated imidacloprid applications have led to resistance development.{{Cite journal |last1=Cui |first1=Li |last2=Qi |first2=Haoliang |last3=Yang |first3=Daibin |last4=Yuan |first4=Huizhu |last5=Rui |first5=Changhui |date=2016-09-01 |title=Cycloxaprid: A novel cis-nitromethylene neonicotinoid insecticide to control imidacloprid-resistant cotton aphid (Aphis gossypii) |url=https://linkinghub.elsevier.com/retrieve/pii/S0048357516300128 |journal=Pesticide Biochemistry and Physiology |series=Insecticide Toxicology in China |volume=132 |pages=96–101 |doi=10.1016/j.pestbp.2016.02.005 |pmid=27521919 |bibcode=2016PBioP.132...96C |issn=0048-3575|url-access=subscription }}
Neonicotinoids represent the most commonly used class of insecticides globally, valued for their effectiveness against a wide spectrum of insect pests, particularly those in the orders Coleoptera, Diptera, and Lepidoptera.{{Cite journal |last1=Jeschke |first1=Peter |last2=Nauen |first2=Ralf |last3=Schindler |first3=Michael |last4=Elbert |first4=Alfred |date=2011-04-13 |title=Overview of the Status and Global Strategy for Neonicotinoids |url=https://pubs.acs.org/doi/10.1021/jf101303g |journal=Journal of Agricultural and Food Chemistry |language=en |volume=59 |issue=7 |pages=2897–2908 |doi=10.1021/jf101303g |pmid=20565065 |bibcode=2011JAFC...59.2897J |issn=0021-8561|url-access=subscription }} Their applications span both agricultural crop protection and animal health, with common usage methods including plant, soil, and seed treatments.{{Cite journal |last1=Elbert |first1=Alfred |last2=Haas |first2=Matthias |last3=Springer |first3=Bernd |last4=Thielert |first4=Wolfgang |last5=Nauen |first5=Ralf |date=November 2008 |title=Applied aspects of neonicotinoid uses in crop protection |url=https://onlinelibrary.wiley.com/doi/10.1002/ps.1616 |journal=Pest Management Science |language=en |volume=64 |issue=11 |pages=1099–1105 |doi=10.1002/ps.1616 |pmid=18561166 |issn=1526-498X|url-access=subscription }} However, ecological concerns have emerged regarding their environmental impact.{{Cite journal |last1=Hladik |first1=Michelle L. |last2=Main |first2=Anson R. |last3=Goulson |first3=Dave |date=2018-03-20 |title=Environmental Risks and Challenges Associated with Neonicotinoid Insecticides |url=https://pubs.acs.org/doi/10.1021/acs.est.7b06388 |journal=Environmental Science & Technology |language=en |volume=52 |issue=6 |pages=3329–3335 |doi=10.1021/acs.est.7b06388 |pmid=29481746 |bibcode=2018EnST...52.3329H |issn=0013-936X}}{{Cite journal |last1=Main |first1=Anson R. |last2=Webb |first2=Elisabeth B. |last3=Goyne |first3=Keith W. |last4=Mengel |first4=Doreen |date=July 2018 |title=Neonicotinoid insecticides negatively affect performance measures of non-target terrestrial arthropods: a meta-analysis |url=https://esajournals.onlinelibrary.wiley.com/doi/10.1002/eap.1723 |journal=Ecological Applications |language=en |volume=28 |issue=5 |pages=1232–1244 |doi=10.1002/eap.1723 |pmid=29603486 |bibcode=2018EcoAp..28.1232M |issn=1051-0761|url-access=subscription }} Studies have documented that imidacloprid, a prominent neonicotinoid, can adversely affect various non-target organisms.{{Cite journal |last1=Kobashi |first1=Koji |last2=Harada |first2=Takaaki |last3=Adachi |first3=Yoshihiro |last4=Mori |first4=Miho |last5=Ihara |first5=Makoto |last6=Hayasaka |first6=Daisuke |date=2017-04-01 |title=Comparative ecotoxicity of imidacloprid and dinotefuran to aquatic insects in rice mesocosms |url=https://www.sciencedirect.com/science/article/abs/pii/S0147651316305383 |journal=Ecotoxicology and Environmental Safety |volume=138 |pages=122–129 |doi=10.1016/j.ecoenv.2016.12.025 |pmid=28040617 |bibcode=2017EcoES.138..122K |issn=0147-6513|url-access=subscription }} These effects include impacts on pollinators and beneficial arthropods, manifesting in behavioral changes, population decline, reduced reproductive success, and increased mortality. Research has also revealed broader ecological consequences, including negative effects on aquatic macroinvertebrates, plankton, crayfish, and mollusks. Furthermore, studies have identified ecosystem-level impacts, such as disruption of songbird migration patterns and decreases in fishery productivity. These findings have motivated the development of alternative insecticides that maintain pest control efficacy while reducing environmental impact.
Mechanism of action
Cycloxaprid’s mode of action was initially believed to be analogous to that of imidacloprid, likely impacting nicotinic acetylcholine receptors{{Cite journal |last1=Shao |first1=Xusheng |last2=Swenson |first2=Tami L. |last3=Casida |first3=John E. |date=2013-08-21 |title=Cycloxaprid Insecticide: Nicotinic Acetylcholine Receptor Binding Site and Metabolism |url=https://pubs.acs.org/doi/10.1021/jf4030695 |journal=Journal of Agricultural and Food Chemistry |language=en |volume=61 |issue=33 |pages=7883–7888 |doi=10.1021/jf4030695 |pmid=23889077 |bibcode=2013JAFC...61.7883S |issn=0021-8561|url-access=subscription }}{{Cite journal |last1=Ohno |first1=Ikuya |last2=Tomizawa |first2=Motohiro |last3=Durkin |first3=Kathleen A. |last4=Naruse |first4=Yuji |last5=Casida |first5=John E. |last6=Kagabu |first6=Shinzo |date=2009-03-16 |title=Molecular Features of Neonicotinoid Pharmacophore Variants Interacting with the Insect Nicotinic Receptor |url=https://pubs.acs.org/doi/10.1021/tx800430e |journal=Chemical Research in Toxicology |language=en |volume=22 |issue=3 |pages=476–482 |doi=10.1021/tx800430e |pmid=19178134 |issn=0893-228X|url-access=subscription }}{{Cite journal |last1=Talley |first1=Todd T. |last2=Harel |first2=Michal |last3=Hibbs |first3=Ryan E. |last4=Radić |first4=Zoran |last5=Tomizawa |first5=Motohiro |last6=Casida |first6=John E. |last7=Taylor |first7=Palmer |date=2008-05-27 |title=Atomic interactions of neonicotinoid agonists with AChBP: Molecular recognition of the distinctive electronegative pharmacophore |journal=Proceedings of the National Academy of Sciences |language=en |volume=105 |issue=21 |pages=7606–7611 |doi=10.1073/pnas.0802197105 |doi-access=free |issn=0027-8424 |pmc=2396707 |pmid=18477694|bibcode=2008PNAS..105.7606T }}
However, the exact mode of action is not fully understood.{{Cite journal |last1=Cui |first1=Li |last2=Sun |first2=Lina |last3=Yang |first3=Daibin |last4=Yan |first4=Xiaojing |last5=Yuan |first5=Huizhu |date=November 2012 |title=Effects of cycloxaprid, a novel cis -nitromethylene neonicotinoid insecticide, on the feeding behaviour of Sitobion avenae |url=https://onlinelibrary.wiley.com/doi/10.1002/ps.3333 |journal=Pest Management Science |language=en |volume=68 |issue=11 |pages=1484–1491 |doi=10.1002/ps.3333 |pmid=22707457 |issn=1526-498X|url-access=subscription }}{{Cite journal |last1=Chang |first1=Xiaoli |last2=Yuan |first2=Yongda |last3=Zhang |first3=Tianshu |last4=Wang |first4=Dongsheng |last5=Du |first5=Xingbin |last6=Wu |first6=Xiangwen |last7=Chen |first7=Haixia |last8=Chen |first8=Yaozhong |last9=Jiao |first9=Yuetong |last10=Teng |first10=Haiyuan |date=2015 |title=The Toxicity and Detoxifying Mechanism of Cycloxaprid and Buprofezin in Controlling Sogatella furcifera (Homoptera: Delphacidae) |url=https://academic.oup.com/jinsectscience/article-lookup/doi/10.1093/jisesa/iev077 |journal=Journal of Insect Science |language=en |volume=15 |issue=1 |pages=98 |doi=10.1093/jisesa/iev077 |issn=1536-2442 |pmc=4677492 |pmid=26175461}}