Design, synthesis, computational profiling, 3D-QSAR, molecular docking of imidazole-pyrazolone scaffolds as dual-action microbial and larvicidal agents: probing structure–activity relationships, ADMET, LD₅₀ for multi-target efficacy

This study aims to expand solvent-free modelling characterisation for imidazole clubbed pyrazolone scaffolds. Computational studies have been carried out on a series of synthesised compounds to evaluate different molecular parameters using the 6–311 +  + G(d,p) basis set in Gaussian 09 software. The biological activity spectrum of a compound has been studied using a structure-based online prediction software (PASS) to estimate the probable biological activity, pharmaco therapeutic effects, biochemical mechanisms and toxicity for compounds. Antibacterial and antifungal activity was evaluated by disc diffusion meta-analysis of compounds which showed mild activity towards E. coli, S. typhi, P. vulgaris, P. aeruginosa, and C. albicans showing promising microbial activities. QSAR models have been adopted for prediction of potential toxicity with statistical validation matrices. Molecular docking studies showed good interaction in terms of binding affinity, inhibition constant and dissociation constant for different proteins. Larvicidal activity tested against Tribolium castaneum showed high mortality activity with a lethal concentration of 0.4892 associated with compound 3c and 3d with concentrations ranging from 2 to 8 ppm respectively. Pharmacokinetic studies were carried out using the eggshell model. The Swiss ADME web tool to understand physiologically based remodelling, modelling or physiologically based bio pharmaceutics modelling (PBBM). An in silico integrated approach combined with biological assays and computational analysis to predict acute toxicity (LD₅₀) of a series of synthesized compounds.