Tetrahydropiperine emerges as a promising scaffold for the development of selective, safe, and effective larvicidal agents by integrating in silico molecular docking and experimental bioassays, and that its saturation enhances larvicidal selectivity while reducing systemic toxicity.
Abstract
The increasing resistance of Aedes aegypti L. to conventional larvicides has intensified the search for novel bioactive compounds through molecular design. This study explores the larvicidal efficacy and toxicological profiles of piperine and its saturated analog, tetrahydropiperine, by integrating in silico molecular docking and experimental bioassays. Both compounds were subjected to docking studies using as target enzymes human and insect acetylcholinesterases (PDB: 4EY6 and 6XYU) and the juvenile hormone-binding protein (PDB: 5V13). Tetrahydropiperine exhibited higher binding affinities, with binding energies of -9.36 kcal.mol-1 (4EY6), -9.32 kcal.mol-1 (6XYU), and -10.60 kcal.mol-1 (5V13), compared to piperine, which showed energies of -9.56, -10.83, and -10.49 kcal.mol-1, respectively. In larvicidal bioassays, tetrahydropiperine demonstrated greater activity, with an LC50 of 54.5 μΜ, whereas piperine showed an LC50 of 78.8 μΜ after 24 hours of exposure. Toxicological evaluation in Swiss mice revealed that tetrahydropiperine, at 300 mg.kg-1, caused no significant adverse effects, while piperine induced mortality and behavioral alterations at doses above 50 mg.kg-1. These results suggest that the unsaturation in piperine side chain may act as a toxicophoric moiety, and that its saturation enhances larvicidal selectivity while reducing systemic toxicity. Tetrahydropiperine thus emerges as a promising scaffold for the development of selective, safe, and effective larvicidal agents.
Biochemical evaluation of triazinone 3 revealed significant reductions in acetylcholinesterase activity and in total protein, carbohydrate, and lipid contents compared with untreated larvae, indicating that larval mortality was accompanied by cholinergic disturbance and depletion of metabolic reserves.
E. El‐Helw, Mahmoud Kamal, Eslam M. Hosni et al.· Bioorganic chemistry (Print)· 0 citations
The mosquito Aedes aegypti is the main vector of dengue, Zika, and Chikungunya, diseases that affect millions of people annually in the Americas. Control of this vector relies mainly on the use of synthetic insecticides, which present limitations related to resistance development and environmental impacts. In this context, β-carboline alkaloids present in Banisteriopsis caapi have attracted interest due to their neurotoxic activity in insects, suggesting potential larvicidal applications. This study aimed to isolate harmine from B. caapi leaves and evaluate its larvicidal activity against A. aegypti. Dried leaves were subjected to sequential maceration with hexane, ethyl acetate, and ethanol. Harmine purification was carried out using column chromatography and preparative chromatography. Structural identification was confirmed by high-resolution mass spectrometry (LC-HRMS/MS) and proton and carbon-13 nuclear magnetic resonance spectroscopy (¹H and ¹³C NMR). Larvicidal bioassays were conducted using third-instar A. aegypti larvae following a protocol adapted from the World Health Organization (WHO). The crude extracts showed mortality rates of 3% for the hexane extract, 7% for the ethyl acetate extract, and 67% for the ethanolic extract. Isolated harmine showed a mortality rate of 40%. These results demonstrate the moderate potential of harmine as a natural larvicide against A. aegypti, providing a basis for further investigations and for the development of bioinsecticides derived from Amazonian resources.
Fernanda Dias Viana, Andrei da Silva Alexandre, R. Roque et al.· Scientia Generalis· 0 citations
Tetranychus cinnabarinus, a prominent mite in agricultural crops, has developed escalating resistance as a result of extensive and repeated chemical pesticide application. Consequently, it remains a quite urgent goal to identify novel structures with high efficacy to reduce resistance. In this study, a series of novel piperidine pyrimidinamine derivatives were designed and synthesized by employing the intermediate derivatization method (IDM) and then screened for their acaricidal activity. Bioassays indicated that most of the target compounds exhibited some acaricial activities against T. cinnabarinus; especially, the lead compounds 15 and 23 displayed excellent acaricidal activity with an LC50 of 1.55 mg/L and 1.46 mg/L, respectively, significantly better than the commercialized acaricide pyridaben. Their structure-activity relationship was discussed, and the field tests were also conducted. It was concluded that lead compounds 15 and 23 with a novel structure and excellent acaricidal potency were worthy of being further optimized for a promising agrochemical acaricide candidate.
Jinlong Yang, A. Guan, Xiaoxi Fan et al.· Journal of Agricultural and...· 0 citations
Neea theifera (Nyctaginaceae) is a poorly explored species with potential pharmacological and agrochemical relevance. The aim of this study was to characterize the volatile chemical composition and biological activities of n-hexane extract from N. theifera leaves (HE-NT), examining both antileishmanial and antibacterial potential. Chemical profiling by GC-MS and GC-FID indicated a terpene-rich extract predominantly composed of β-pinene (21.3%), 1,8-cineole (17.7%), and β-caryophyllene (15.4%). The extract exhibited marked antileishmanial activity against Leishmania (L.) infantum promastigotes, with IC50 values of 10.05 μg/ml (24 hr) and 3.45 μg/ml (48 hr). Due to this pronounced activity, molecular docking against L. infantum trypanothione reductase (TryR) was performed to provide computational support for the observed in vitro findings. Antibacterial assays using broth microdilution demonstrated significant activity against Actinomyces naeslundii and the phytopathogens Xanthomonas citri and X. campestris, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 50 to 62.5 μg/ml. These findings collectively expand the phytochemical knowledge of N. theifera and identify this species as a promising source of bioactive terpenoids for future antiparasitic and antibacterial research.
Gleiciane C. S. Pereira, Jaciel G Dos Santos, C. Fernandes et al.· Journal of Toxicology and En...· 0 citations
Hemiptera pests damage crops and transmit viruses through piercing-sucking mouthparts, causing enormous economic losses and inducing resistance to insecticides. Novel insecticides are critical to combat rising resistance. Nicotinamidase, a newly validated target present in the insect chordotonal organ, has attracted attention. A series of novel sulfonyl, carbonyl, and amide group-based 4-(trifluoromethyl)nicotinamide derivatives was designed using the prodrug strategy and an intermediate derivatization method. Bioactivity assays indicated that most compounds possessed enhanced insecticidal activity. B-38 exhibited outstanding lethality against Sitobion avenae (LC50 = 0.710 mg/L), outperforming that of flonicamid (LC50 = 13.7 mg/L). The 3D-QSAR model revealed that the introduction of electron-withdrawing groups at the R3 position and electron-donating groups at the R4 positions, respectively, enhanced insecticidal potency. DFT calculations suggested that propargyl and imide groups may be essential for bioactivity. This study provides fundamental insights for developing green and efficient insecticides.
Ying Bian, Li-Xia Zhao, Tiansong Li et al.· Journal of Agricultural and...· 0 citations
In the pursuit of novel insecticidal agents, a series of new thieno[2,3-b]quinoline derivatives were synthesized via efficient and versatile routes, starting from ethyl 3-aminothieno[2,3-b]quinoline-2-carboxylate. The synthesized compounds including hydrazone (8a–c), arylidene (9a–c), and pyrano[3,2-c]thieno[2,3-b]quinoline (10a–c) derivatives were characterized using FT-IR, NMR, and mass spectrometry. Their insecticidal efficacy was evaluated against both nymph and adult stages of Aphis fabae, with median lethal concentration (LC50) values determined through probit analysis. Compound 10b exhibited the highest potency, with LC50 values of 0.117 mg/L (nymphs) and 0.366 mg/L (adults), approaching the activity of the commercial insecticide acetamiprid. Molecular docking studies against the Aplysia californica acetylcholine-binding protein (AChBP, PDB: 3SQ6), a surrogate for insect nicotinic acetylcholine receptors, revealed strong binding affinities for the pyranothienoquinoline derivatives, particularly 10b (−7.30 kcal/mol), supported by multiple hydrogen bonds and hydrophobic interactions with key residues. These findings underscore the potential of the pyrano[3,2-c]thieno[2,3-b]quinoline scaffold as a promising candidate for the development of new, target-specific insecticides.
Mokhtar A Abdul-Malik, A. K. Kamal El‐dean, Abdel Haleem M. Hussein et al.· ACS Omega· 0 citations
