[BMIM]OAc promoted one-pot synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidin-5-ones and their antimicrobial activity

Abstract

A one-pot method was developed for synthesizing pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidin-5-ones using the recyclable ionic liquid catalyst [BMIM]OAc in ethanol under reflux conditions. This approach achieved high yields (76–95%) across various substrates along with straightforward product isolation and catalyst recyclability. The synthesized compounds 4(a–l) were tested for antimicrobial activity against Gram-positive and Gram-negative bacteria, and fungal strains. Notably, compounds 4c and 4e showed strong antibacterial effects against S. aureus (MIC: 8 µg mL⁻¹), while 4a, 4b, and 4f effectively inhibited E. coli (MIC: 8 µg mL⁻¹). Compound 4l exhibited notable antifungal activity against C. albicans (MIC: 8 µg mL⁻¹), outperforming the standard drugs. Cytotoxicity assessment on HEK293 cells revealed low toxicity in most derivatives (IC₅₀ > 50 µM), with halogenated analogs (4c, 4e) displaying moderate activity but remaining less toxic than doxorubicin. Molecular docking and dynamics simulations confirmed stable interactions of key compounds (4c, 4e, 4f) with bacterial Tet repressor class D and fungal sterol 14-α demethylase, consistent with experimental data. Overall, this ionic liquid-catalyzed approach provides an efficient route to bioactive heterocycles with promising antimicrobial and anticancer potential.