Novel Chalcone Derivatives Containing Pyridone and Thiazole Moieties: Design, Synthesis, Molecular Docking, Antibacterial, and Antioxidant Activities

Abstract: A new series of chalcones 4a-i; 6a,b, and 8 was synthesized from the condensation of ketone 2, which was prepared from the reaction of thiourea derivative 1 with 3- chloropentane-2,4-dione in MeOH at reflux temperature, with substituted aromatic/ heterocycle aldehydes in EtOH containing NaOH at room temperature. Antimicrobial and antioxidant activities were assessed for the synthesized compounds. The antimicrobial susceptibility tests revealed that compounds (4c, 4e, 4f, and 4i) exhibited good to excellent activity against C. albicans, S. aureus ATCC25923, E. faecalis ATCC29212, P. aeruginosa ATCC10145, and S. mutans ATCC25175. The antioxidant capabilities were assessed using the DPPH and ABTS radical scavenging methods. Compounds (4b, 4c, 4d, and 4e) proved to be better at scavenging DPPH and ABTS. This study involved in-silico drug-likeness and physicochemical properties and evaluated their ADMET profiles. According to the results of the molecular docking simulation, the synthesized compounds showed lower binding energy at the active sites of Dihydropteroate synthase, Sortase A, LasR, and Penicillin-binding protein pockets, which suggests that they may have an inhibitory effect on the enzymes and show promise as antimicrobial agents.