Synthesis, crystal structure, and antiviral evaluation of new imidazopyridine-schiff base derivatives: in vitro and in silico anti-HIV studies†

A series of Imidazo[1,2-a]pyridine-Schiff base derivatives were synthesized and characterized using ¹H NMR, ¹³C NMR, Mass Spectrometry and FTIR techniques, and the structure of 4a was further confirmed through single-crystal X-ray diffraction analysis. Density Functional Theory (DFT) has been used to investigate the structural and electronic properties. The synthesized compounds were evaluated in vitro for their antiviral activity against human immunodeficiency virus type-1 (HIV-1) and human immunodeficiency virus type-2 (HIV-2) in MT-4 cells. Compound 4a displayed EC₅₀ values of 82,02 and 47,72 μg ml⁻¹ against HIV-1 and HIV-2, respectively. Molecular docking studies were conducted to gain insights into the interaction mechanism of the synthesized compounds with HIV-1 reverse transcriptase. ADME analysis suggested acceptable pharmacokinetic profiles, though solubility remains a limitation for these compounds, highlighting the need for further structural modifications to enhance bioavailability and therapeutic potential.