Synthesis, insecticidal Activity, and molecular docking analysis of some benzo[h]quinoline derivatives against Culex pipiens L. Larvae

• Published in: Bioorganic chemistry 2024-09, Vol.150, p.107591, Article 107591
• Main Authors: El-Helw, Eman A.E., Hosni, Eslam M., Kamal, Mahmoud, Hashem, Ahmed I., Ramadan, Sayed K.
• Format: Article
• Language: English
• Subjects: 2(3H)-Furanone; Acetylcholinesterase - metabolism; Animals; Benzo[h]quinoline; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Culex - drug effects; Culex pipiens larvae; Dose-Response Relationship, Drug; Insecticidal activity; Insecticides - chemical synthesis; Insecticides - chemistry; Insecticides - pharmacology; Larva - drug effects; Molecular Docking Simulation; Molecular Structure; Mosquito control; Pyrrolinone; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Structure-Activity Relationship; Thiation
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2024.107591

The ADME (absorption, distribution, metabolism, and excretion) analyses displayed its desirable drug-likeness and oral bioavailability properties. [Display omitted] •Heterocycles bearing a benzo[h]quinoline moiety were synthesized from a 3-((2-chlorobenzo[h]quinolin-3-yl)methylene)-furan-2(3H)-one.•The insecticidal activity of these compounds was evaluated against mosquito larvae (Culex pipiens L.).•In silico docking analysis revealed that these compounds may act as AChE inhibitors.•Interactions with nicotinic acetylcholine receptors and sodium channel alpha subunits were also investigated.•The results reflected potential of benzo[h]quinolines as promising for developing effective mosquito control strategies. Some heterocycles bearing a benzo[h]quinoline moiety were synthesized through treating a 3-((2-chlorobenzo[h]quinolin-3-yl)methylene)-5-(p-tolyl)furan-2(3H)-one with four nitrogen nucleophiles comprising ammonium acetate, benzylamine, dodecan-1-amine, and 1,2-diaminoethane. Also, thiation reactions of furanone and pyrrolinone derivatives were investigated. The insecticidal activity of these compounds against mosquito larvae (Culex pipiens L.) was evaluated. All tested compounds exhibited significant larvicidal activity, surpassing that of the conventional insecticide chlorpyrifos. In silico docking analysis revealed that these compounds may act as acetyl cholinesterase (AChE) inhibitors, potentially explaining their larvicidal effect. Additionally, interactions with other neuroreceptors, such as nicotinic acetylcholine receptor and sodium channel voltage-gated alpha subunit were also predicted. The results obtained from this study reflected the potential of benzo[h]quinoline derivatives as promising candidates for developing more effective and sustainable mosquito control strategies. The ADME (absorption, distribution, metabolism, and excretion) analyses displayed their desirable drug-likeness and oral bioavailability properties.