Synthesis, characterization, antimicrobial evaluation, pharmacokinetic and QSAR studies of some novel acrylates: in vitro and in silico approach

Novel acrylate derivatives ( 1-4) were synthesized by Knoevenagel condensation of thiophene-2-carbaldehyde with malononitrile, cyanoacetamide, ethyl cyanoacetate and isobutyl cyanoacetate in the presence of ammonium acetate (NH 4 OAc) using microwave irradiation under solvent-free conditions. The reactions were completed in 30 sec with excellent yield. All the synthesized compounds were characterized by FT-IR, and NMR ( 1 H, 13 C, DEPT-135) analyses. The biological assays revealed that analog 3 had the highest antibacterial activity against Salmonella typhi (7.5 ± 0.33 mm), while analog 2 demonstrated the strongest antifungal effect against Aspergillus niger (90.33 ± 0.23 mm) and Aspergillus flavous (89.55 ± 0.33 mm). Some analogs exhibited no activity against Staphylococcus hominis and Shigella flexneri . Additionally, molecular docking studies indicated that analog 4 had the strongest interaction with the fungal receptor ( PDB: 5V5Z ), supporting the observed biological activities. The molecular dynamics simulation was performed against Lanosterol 14-alpha demethylase (LDM) (PDB ID: 5V5Z; organism: Candida albicans ) to investigate the binding stability and interactions between the drug and targeted protein. The outcome of the antimicrobial activity and in-silico analysis assessment of the compounds demonstrated significant effectiveness, supporting their selection as potential antifungal drug candidates.