article · Arabian Journal of Chemistry
Researchers evaluated a series of spiropyrazoline indolin-3-one congeners for their antimicrobial and antioxidant properties, supported by computational studies. The compounds demonstrated moderate to excellent antimicrobial activity against various microbial strains, including bacteria and fungi, with efficacy dependent on the chemical structure's aromatic ring substituents. They also showed dose-dependent antioxidant activity, with specific congeners exhibiting remarkable effects due to electron-donating groups. Computational analyses, including density functional theory, molecular docking, and molecular dynamics simulations, helped explain the observed activities and confirmed stable binding with target proteins. Further analyses suggested these compounds possess good oral bioavailability and pharmacokinetics without apparent toxicity, indicating their potential for future drug development.
This research identifies new chemical compounds with promising antimicrobial and antioxidant properties. Understanding their mechanisms and favourable drug-like characteristics could lead to the development of novel therapeutic agents to combat infections and oxidative stress, addressing significant health challenges.
This early-stage research identifies novel spiropyrazoline oxindole congeners with potential as new antimicrobial and antioxidant agents. The findings on good oral bioavailability and pharmacokinetics suggest these compounds could be candidates for further drug discovery and development programmes. Potential users include pharmaceutical companies and research organisations seeking to develop new medicines for infectious diseases and conditions related to oxidative stress.
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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.
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DOI: 10.1016/j.arabjc.2023.105465
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