Synthesis, Characterization, In vivo, Molecular Docking, ADMET and HOMO-LUMO study of Juvenile Hormone Analogues having sulfonamide feature as an Insect Growth Regulators

Abstract

The search for a simple and efficient method for the synthesis of sulfonamide derivatives as an Insect Growth Regulators (IGRs) under mild and eco-friendly conditions is of our interest. Here, we report a simple, efficient, and eco-friendly method for the synthesis of sulfonamide derivatives. A series of sulfonamides containing aniline derivatives have been synthesized. L-amino acid has been added in the intermediate steps which increase the bioactivity of the synthesized analogs. The structure elucidations of the synthesized analogs have been done using spectroscopic tools like - FTIR, NMR-1H, 13C, ESI-MS. In vivo efficacy of the synthesized analogs has been investigated under laboratory conditions. Galleria mellonella has been chosen as a model insect, commonly known as honeycomb pest. G. mellonella causes a huge loss to beekeeping industries. All synthesized analogs showed insect growth regulatory action against the model species. Calculated LC50 and LC90 of all the analogs (T1-T8) against the fourth instar larvae were 9.99, 10.12, 13.70, 13.59, 13.94, 21.69, 13.28, 12.80 ppm and 153.27, 131.69, 113. 23, 161.70, 141.48, 205.75, 110.93, 96.91 ppm, respectively. Among these analogs, N-(1-isopropyl-2-oxo-2- p-nitroanilino-ethyl) toluene-p-sulphonamide (T8) and N-(1-isopropyl-2-oxo-2- p-nitroanilino-ethyl) benzene-sulphonamide (T7) exhibited the good pest larval mortality in comparison to in use IGR like- Pyriproxyfen (T1) and Fenoxycarb (T2). Docking using AutoDock 4.2 has been carried out to identify the potential binding affinities and mode of interaction of the synthesized analogs (T3-T8) with Juvenile Hormone Binding Protein (JHBP) of G. mellonella in comparison to in use IGRs Pyriproxyfen (T1) and Fenoxycarb(T2). Additionally, in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtration has been used to predict the properties of the analogs. Quantum chemical calculations like Density Functional Theory have been performed to calculate different global reactivity descriptors. A small difference between HOMO and LUMO energy signifies the electronic excitation energy which is essential to calculate molecular reactivity and stability of the aniline based sulfonamides (T3-T8).