Synthesis, biological activities evaluation, density functional theory investigation, and molecular docking studies of hydroxybutyl and hydroxypropyl aminophosphonic Acids”

Abstract

This PhD thesis focuses on the design, synthesis, and evaluation of new α-aminophosphonic acids (HAP1 and HAP2) as promising bioactive compounds. It begins with a comprehensive review of organophosphonates, emphasizing their importance in medicinal chemistry due to the stability of the carbon–phosphorus (C–P) bond, which allows them to mimic biological phosphates and act as enzyme inhibitors. The experimental work involves the synthesis of the target compounds, followed by their characterization using techniques such as FT-IR, UV-Vis, and NMR spectroscopy. In addition, computational studies based on Density Functional Theory (DFT) and molecular docking were conducted to understand their structural, electronic, and biological interactions, alongside ADME-T predictions to evaluate their pharmacokinetic and toxicity profiles. The biological investigations demonstrated that the synthesized compounds exhibit significant antioxidant activity, supported by multiple assays (DPPH, ABTS, FRAP), as well as synergistic effects when combined with standard antioxidants. Furthermore, they showed antibacterial properties and enzyme inhibition potential. A key innovation of this work lies in the incorporation of these compounds into hyaluronic acid-based nanohydrogels, enabling controlled drug release, improved stability, and enhanced bioavailability. Overall, this study highlights the potential of α-aminophosphonic acids as valuable candidates in pharmaceutical development, particularly when integrated with nanotechnology-based delivery systems.