Unlocking the biological potential of novel imidazo[2,1-b] thiazole–2,3-dihydrofuran hybrids: Insights from computational studies

Novel imidazo[2,1- b ] thiazole-conjugated trans -2,3-dihydrofuran analogues were successfully synthesized through an efficient one-pot multicomponent cyclization strategy involving imidazo[2,1- b ] thiazole-5-carbaldehyde, dimedone, and phenacyl bromide. The reaction was carried out in acetonitrile using pyridine as the catalyst and triethylamine as the base, affording the desired hybrid derivatives in good to excellent yields under mild reaction conditions. The structures of the synthesized compounds were comprehensively characterized by 1 H and 13 C NMR nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and infrared (IR) spectroscopy. The synthesized derivatives (4a-4i) were subsequently screened for their anti-oxidant and anti-inflammatory activities. All compounds demonstrated appreciable DPPH radical-scavenging activity, exhibiting percentage inhibition values in the range of 43.5–53.6% at the highest tested concentration (200 μg/mL). Among the evaluated compounds, derivative 4a , bearing dichloro substituents on the aromatic rings, exhibited remarkable anti-inflammatory potential with 95.05% inhibition, surpassing the activity of the reference drug celecoxib (81.66%). Furthermore, molecular docking investigations were performed to explore the binding interactions of the synthesized compounds with the target proteins, namely PDB ID: 1N3U and cyclooxygenase-2 (COX-2; PDB ID: 3LN1 ). The docking analyses revealed favorable binding affinities and significant molecular interactions within the active sites of the target proteins, providing valuable mechanistic insights into their biological activities. These findings offer a rational framework for the future design and optimization of imidazo[2,1- b ] thiazole-based hybrids as promising therapeutic candidates.