In vitro and in silico evaluation of the antimicrobial and antioxidant activities of spiropyrazoline oxindole congeners

The search for novel powerful antimicrobial and antioxidant agents is considered a dynamic field in medicinal chemistry. In this context, a series of spiropyrazoline indolin-3-one congeners were assessed for their in vitro bioactivities, and in-silico studies were conducted to support the experimental results. The antimicrobial screening of the spiropyrazoline oxindole congeners against the selected microbe strains (Staphylococcus aureus (CECT 976), Bacillus subtilis (DSM 6633), Escherichia coli (K12), and Candida albicans (ATCC 10231)) exhibited moderate to excellent, compared to control standard antibiotics (Ampicillin, streptomycin and fluconazole). This activity was observed to be tightly dependent upon the nature of the substituents carried by the aromatic rings. Moreover, the tested compounds showed variable dose -dependent antioxidant activity. Notably, congeners 2c, 2d and 2e exhibited a remarkable antioxidant activity, due to the positive impact of the electron-donating groups (CH3 and OCH3) on the antioxidant activity. Density functional theory (DFT) simulations were executed on the target molecules to better understand their structural and electronic properties, as well as to explain the results obtained from the antioxidant activity. The molecular docking studies showed that the studied congeners have good binding affinities and interactions with the target proteins (catalase compound II and CYP51). Moreover, the 100 ns molecular dynamics (MD) simulation analysis was conducted to follow the behavior of the complexes formed between ligand 2e and the target proteins (2CAG and 5V5Z) under in-silico physiological conditions to explore and evaluate its stability over time. MD simulation indicated a stable conformation and binding patterns in a stimulating environment of the congeners (2CAG-2e and 5V5Z-2e). The results of Petra/Osiris/Molinspiration (POM) analyses suggested that all the spiranic cycloadducts have good oral bioavailability and pharmacokinetics without any evidence of observed toxicity. Taken together, our findings provide valuable experimental and theoretical information that will be helpful for designing novel spiranic molecules with potential pharmacological applications.