Discovery of new molecular hybrid derivatives with coumarin scaffold bearing pyrazole/oxadiazole moieties: Molecular docking, POM analyses, in silico pharmacokinetics and in vitro antimicrobial evaluation with identification of potent antitumor pharmacophore sites

Abstract

This synthetic organic methodology involves the creation of novel coumarin-based hybrids of series (1-4) with pyrazole ring and (5-8) with oxadiazole moiety. The targeted compounds were tested for In vitro Antimicrobial efficacy against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans pathogenic microbes using disc diffusion and broth microdilution with ciprofloxacin and fluconazole as reference standards. 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 (ΔE), global hardness (η), global softness (S), and ionisation potential (IP) and FMOs, NBOs, MEP, and Mulliken Charge analysis. The POM tests found three integrated pharmacophore sites with antibacterial, antiviral, and anticancer activities. Molecular docking studies are also used to determine the S. aureus nucleoside diphosphate kinase receptor's affinity and mode of action for the synthesized drugs. In silico analysis of thermodynamic and therapeutic effectiveness properties, including Lipinski's 'rule of five', Veber's rule, and ADME properties, predicted toxicity-free, non-carcinogenic, and risk-free oral administration of the synthesized complexes.

Keywords: Coumarin; Density functional theory; In vitro Antimicrobial; Molecular Docking: POM analysis; Oxadiazole moieties.