Green synthesis of tetrahydropyridine-3-carboxylate derivatives and evaluation of antimicrobial and antimalarial activities supported by molecular docking, POM studies, and drug-likeness analysis

A series of novel haloarene-decorated tetrahydropyridine derivatives B(1a–1f) were synthesized via a simple, environmentally benign one-pot multicomponent reaction employing ethanol as a green solvent and [Et₃NH][HSO₄] as a Brønsted acid ionic liquid catalyst. The reaction utilized methyl acetoacetate (1 mmol), substituted aromatic aldehydes (2 mmol), and substituted anilines (2 mmol) at 60 °C to afford the desired compounds. All compounds were evaluated for their in vitro antimicrobial activity against three fungal strains ( Candida albicans , Aspergillus niger , and Aspergillus clavatus ), two Gram-negative bacteria ( Escherichia coli and Pseudomonas aeruginosa ), and two Gram-positive bacteria ( Staphylococcus aureus and Streptococcus pyogenes ), using the serial broth dilution method. Additionally, their antimalarial potential was assessed against chloroquine- and quinine-sensitive 3D7 and multidrug-resistant Dd2 strains of Plasmodium falciparum . Among the synthesized derivatives, compounds B1a , B1b , and B1b exhibited the most potent antimicrobial and antimalarial activities. Molecular docking studies revealed that compound B1f showed the highest binding affinity toward S. aureus nucleoside diphosphate kinase, with a predicted free binding energy of − 913 kcal/mol. Pharmacological profiling suggested favorable drug-like properties and non-toxic behavior. These findings highlight haloarene-decorated tetrahydropyridine derivatives as promising dual-action candidates with potential to combat both bacterial and malarial infections.