“Sustainable synthesis and biological evaluation of novel benzo[4,5]imidazo[1,2-a]pyrimidine carboxamide derivatives”

Aim To develop a sustainable synthetic protocol for novel imidazo[1,2-a]pyrimidine derivatives using an ionic liquid catalyst and evaluate their antimicrobial and anticancer potential.Materials and methods Twenty imidazo[1,2-a]pyrimidine derivatives (KTI–1 to KTI–20) were synthesized using a recyclable diisopropylethylammonium heptanoate [DIPEA][C6COO] under solvent-free conditions. Antimicrobial activity, cytotoxicity against the KB-31 oral carcinoma cells, molecular docking, molecular dynamics simulations, and in silico Absorption, Distribution, Metabolism, Excretion, Toxicity and drug-likeness analyses were performed.Results The optimized method afforded target compounds in 87 − 94% yields within 6 − 9 min. Selected compounds showed antimicrobial activity with minimum inhibitory concentration (MIC) values of 15.62 to 31.26 μg/mL, with KTI −2, KTI −13, and KTI −18 being the most active; KTI-2 showed the highest cytotoxicity (IC50 = 41.78 μg/mL). Molecular docking against 6SNU, 1T8I, 1IYL, and 6BHX revealed binding affinities (−10.3 to −6.5 kcal/mol), while molecular dynamics simulations confirmed stability. Key interactions involved Gly293, Lys288, Leu295, Ser291, Thr501, Tyr225, and Ile297. Analyses indicated Lipinski’s compliance, human intestinal absorption of 87.54–90.58%, bioavailability of 0.55, favorable solubility and low predicted toxicity.Conclusion The synthesized derivatives demonstrated promising antimicrobial and anticancer activities supported by computational studies and pharmacokinetics. However, selectivity toward normal cells was not evaluated, and further mechanistic and in vivo studies are required.