Modeling, virtual screening, and enzymatic docking of trehalose 6-phosphate phosphatase and evaluation of the insecticidal effect of phthalimide, N-(p-tolylsulfonyl) on Aedes aegypti (Diptera: Culicidae)

Abstract

BACKGROUND

Aedes aegypti Linnaeus is a medically important vector because of its role in transmitting several arboviruses. Trehalose-6-phosphate phosphatase (TPP), an enzyme from the trehalose pathway, was the focus of this study, which aimed to model it, perform molecular docking and select potential ligands to evaluate their larvicidal and adulticidal activity on the mosquito.

RESULTS

Because no TPP structure for A. aegypti was described, the modeling was done by homology, using the TPP from Mycobacterium tuberculosis Zopf as a template, with 31% similarity. Following virtual screening, a search for TPP-like molecules on PubChem resulted in 227 molecules, and phthalimide, N-(p-tolylsulfonyl) (PNT) was selected and tested in vivo. Larvicidal tests were conducted in 24-well plates, and adulticidal tests used sugar baits with several concentrations (5 to 100 ppm) of PNT. In larval tests, mortality ranged from 38% to 52% at 24 h and reached 92% at 100 ppm PNT after 72 h. Larval mortality progressively increased over 96 h, with estimated lethal concentration (LC₅₀ and LC₉₀) values after 48 h of 18 and 198 ppm respectively. In adulticidal tests, despite high bait uptake, acute ingestion of PNT did not cause mortality in adult mosquitoes.

CONCLUSION

PNT demonstrated larvicidal activity against A. aegypti, suggesting that mosquito TPP could be a target in the search for new-generation insecticides. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.