Synthesis, Characterization, and antiviral evaluation of New Chalcone-Based Imidazo[1,2-a]pyridine Derivatives: Insights from in vitro and in silico Anti-HIV studies.

Given the ease of synthetic accessibility and the promising biological profile demonstrated by both imidazo[1,2-a]pyridine and Chalcone derivatives, a series of Chalcone-based imidazo[1,2-a]pyridine derivatives were synthesized and characterized using H NMR, C NMR, Mass Spectrometry and FTIR techniques. Density functional theory (DFT) was employed to investigate the structural and electronic properties, providing insights into potential reactive sites. The synthesized compounds were evaluated in vitro for their antiviral properties against human immunodeficiency virus type-1 (HIV-1) and human immunodeficiency virus type-2 (HIV-2) in MT-4 cells. Furthermore, Molecular docking studies show strong binding affinities with HIV-1 reverse transcriptase and HIV-2 protease. To further understand the dynamic behavior and stability of these interactions, molecular dynamics (MD) simulations were conducted. The MD results indicated stable binding conformations of the ligands within the active sites, with low RMSD and RMSF values throughout the simulation, confirming the robustness of these interactions. ADME predictions suggested acceptable pharmacokinetic profiles, though solubility remains a limitation for these compounds. Although the in vitro antiviral activity was limited, the combination of in vitro and in silico approaches provided valuable insights, guiding further structural optimization to improve bioavailability and enhance the therapeutic potential of these derivatives.