Repellent activity of trans‐anethole and tea tree oil against Aedes aegypti and their interaction with OBP1, a protein involved in olfaction

Abstract

Mosquitoes act as vectors for the transmission of various infectious pathogens. The associated diseases are prevalent in tropical and subtropical regions of the world and can be prevented by effective vector control and management. Natural compounds have become a potential alternative to synthetic repellents that are unsafe and harmful to the environment. The repellent activity of trans‐anethole and tea tree [Melaleuca alternifolia (Maiden & E. Betche) Cheel, Myrtaceae] oils was tested against the vector Aedes aegypti (L.) (Diptera: Culicidae) by performing a modified arm‐in‐cage and cloth‐patch repellent assay. Tea tree oil [EC50 = 0.002 mg ml−1, 95% confidence interval (CI) = 0.001–0.003] was found to be a more potent repellent than trans‐anethole (EC50 = 0.003 mg ml−1, 95% CI = 0.001–0.007). Tea tree oil was determined to have a complete protection time of 60 min, which was less than N,N‐dimethyl‐3‐methylbenzamide (DEET), which was used as a control (480 min). The binding affinity of trans‐anethole and terpinen‐4‐ol (a major component of tea tree oil) for the protein target AaegOBP1, a component of the olfactory system of Ae. aegypti, was determined using blind and targeted molecular docking. The results of molecular docking were in accordance with the findings of the repellent assay. OBP1 was found to have a better binding affinity for terpinen‐4‐ol (ΔG = −7.1 kcal per mol) than trans‐anethole (ΔG = −6.9 kcal per mol). In addition, a hydrogen bond of 0.1997 nm (1.997 Å) long was formed between PHE123 of OBP1 and terpinen‐4‐ol as established with Mcule. Further detailed analysis and experimentation of natural products as repellents is required as they may replace currently used synthetic repellents – natural repellents generally have less side effects and lower toxicity while being cost‐effective and easily available.

Design, Synthesis, and Biological Evaluation of Pyrido [1,2-α] Pyrimidinone Mesoionic Derivatives Bearing Propenylbenzene as the Vector Control Insecticide

“…7,9,11,38 SARs showed that Propenylbenzene, such as anethole, has a broad range of biological activities against insect vectors, which had been represented in different insecticidal chemistry areas. 16,24 Based on a rationally conceived pharmacophore model, substituted propenylbenzene groups were introduced at the 1-position of the mesoionic core and explored the SAR (Tables 4−6). Although many types of substitutions in the propenylbenzene ring were tolerated, unsubstituted propenylbenzene remained the most potent compounds.…”

“…In order to optimize the mesoionic lead compound, 2,2,2-trifluorethyl and (2-chlorothiazol-5-yl)­methyl group replace the n -propyl group at the 1-position of the mesoionic core based on bioisosteric replacement strategy (compounds 2 and 3 ) showing excellent insecticidal activity against many kinds of pests . Further optimization based on compound 3 led to the discovery of triflumezopyrim ( 4 ) and dicloromezotiaz ( 5 ) as a hemiptera and lepidoptera insecticide by the bioisosteric replacement strategy (Figure ), , which exert their insecticidal action by inhibiting nicotinic acetylcholine receptors (nAChRs). − Also, the nAChRs play a central role in fast excitatory synaptic transmission in the insect central nervous system and have been an important neuronal target for the control of vector insects. , As a highly efficient pharmacophore, anethole has a broad range of biological activities against vector insects, including mosquitoes, − Rhipicephalus microplus, Rhipicephalus annulatus, and Dermacentor nitens, , Myzus persicae, , Musca domestica, Bemisia tabaci, and Periplaneta americana, with neurotoxic actions of acetylcholinesterase, GABA receptors, and octopamine receptors. − It is a potential chemical probe and a lead candidate for the development of insect vector control agents …”