Design, synthesis and antibacterial activity of new Isatin-based Schiff base derivatives: Molecular docking, POM analysis, in silico pharmacokinetics and identification of antitumor pharmacophore sites

Abstract

In this study,we have reported a series of Isatin-based Schiff base derivatives G(1–5), the formation of the synthesized compounds was confirmed by Spectro analytical techniques. The synthesized compounds were screened for antimicrobial activity against Pseudomonas aeruginosa, Salmonella typhie,andStaphylococcus aureusbacterial strainsandantifungalscreening againstCandida albicansusing disc diffusion and broth microdilution with ciprofloxacin and fluconazole as reference standards, which indicated that the studied compounds exhibited exceptional antibacterial properties. The density functional theory (DFT) studies were used to study atomic structure and reactivity, including absolute electronegativity (χ), electrophilicity (ω), electron acceptor (ω+), donor capabilities (ω–), electron affinity (EA), energy gap (∆E), global hardness (η), global softness (S), and ionization potential (IP) and frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), and Mulliken Charge analysis. The Petra, Osiris, and Molinspiration(POM) tests found three integrated pharmacophore sites with antibacterial, antiviral, and anticancer activities. Molecular docking studies are also used to determine theaffinity and mode of action of the synthesized compounds with the targeted receptor, Staphylococcus aureus nucleoside diphosphate kinase receptor, which supported the experimental results. In silico analysis of thermodynamic and therapeutic effectiveness properties, including Lipinski's 'rule of five', Veber's rule, boiled egg model, and ADME properties, forecastthetoxicity-free, non-carcinogenic, and risk-free oral administration of the synthesized complexes.