A Multidimensional Investigation from Electronic Properties to Biological Activity of 2-[(4-Hydroxyphenyl)iminomethyl]thiophene by DFT, HOMO-LUMO, MEP, NLO, NBO, Mulliken, Hirshfeld and Molecular Docking Analyses

Abstract

Ever since they were first discovered, Schiff bases have been the subject of much attention due to their functional chemical character and intensive interdisciplinary applications, particularly in medicinal chemistry. The compounds are gaining interest due to their ability to provide stable coordination complexes and exhibit a vast array of biological activities, such as antimicrobial, anticancer, and antiviral activities. In this contribution, the structure of 2-[(4-hydroxyphenyl)iminomethyl]thiophene, (I), a compound previously described in the literature, was ascertained with great accuracy employing up-to-date quantum chemical calculations to better understand its electronic behavior and reactivity. In addition, the antiviral, anticancer, and anti-Alzheimer activity of the compound was thoroughly investigated employing a battery of in vitro and computational assays. The results proved the active character of the compound against various biological targets, and that it was a multiradial drug candidate. Furthermore, ADME-Tox properties were examined to evaluate the pharmacokinetic profile and toxicity of the compound. Favorable ADME properties and a low likelihood of toxicity highlight the molecule’s suitability for continued development. The research showed the chemical stability of the molecule, its high hyperconjugation and strong intramolecular stability as factors contributing to its overall strength. These structural features also hold out promise for drug development since they can lead to increased efficacy and long-lasting activity in biological systems. Furthermore, molecular docking simulations corroborated the efficacy of the compound as a potential ligand that could interact with key biological macromolecules, rendering it a highly effective ligand with high binding affinity. This also contributes to its potential as a lead compound for new therapeutic drugs. Lastly, this research not only describes the structure and properties of (I), but also provides a pragmatic window through its pharmacological potential, worthy of experimental and clinical studies to explore fully its promise in drug discovery.

Keywords

• Computational quantum methods
• Hirshfeld surface characterization
• Molecular docking
• ADME properties
• Toxicity analysis

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