Synthesis, DFT, molecular docking, and insecticidal evaluation of new pyrazole-thiazole hydrazones derivatives...

By reacting ethyl-3-oxo-2-(2-(p bromo)hydrazono)butanoate (1) with various α-halocarbonyl compounds, such as ethyl 2-chloro-3-oxobutanoate 3 and ethyl 2-chloro-2-(aryldiazenyl) acetate 5a-d, this work produces a new series of pyrazole-thiazole derivatives 4 and 6a-e. The target compounds' structures were determined and reported using ¹H NMR, ¹³C NMR, FT-IR, and ESI-MS spectroscopy. Additionally, the electrical characteristics of the powerful compounds were investigated through computational study using density functional theory (DFT) at the B3LYP/6-31 G (d,p) level. Atomic net charges and frontier molecular orbital energy were examined. The generated thiazole compounds' insecticidal efficacy was evaluated. Over the course of three time intervals12, 24, and 48 h his study assessed the residual toxicity of eight tested chemicals on adult Tribolium castaneum (floor beetles). Mortality rates and LC₅₀ values at each time point were used to evaluate the effectiveness. The results showed that some compounds, particularly compound 4, which had the lowest LC₅₀ of about 0.43 µg/mL, showed strong and quick hazardous effects within 12 h. The hazardous effects grew over time, with 6e showing the highest efficacy at 24 h with an LC₅₀ of roughly 0.01 µg/mL. Finally, proteins were subjected to molecular docking to ascertain the binding affinity of the investigated compounds. The apo target and its complexes with compounds 6b and 6c were each subjected to a 100 ns molecular dynamics simulation. Molecular docking and molecular dynamics simulations demonstrated that the acetylcholine esterase 6b complex maintained significant stability during the simulation periodThis work addresses finding insecticidal structures with innovative scaffolds that should be safe for the environment and have less of an influence on non-target species and human health a hot topic in contemporary pesticide research is essential.