Synthesis, In vitro Antimicrobial, and In Silico Studies of 2-Hydroxy-1, 2-Diphenylethanone Derivatives

Infectious diseases place a significant impact on the healthcare system. It causes 7.7 million fatalities each year, with a disproportionately high burden in sub-Saharan Africa. Drug resistant pathogens attributed to 4.95 million and 1.27 million are illnesses of bacteria that are resistant to the current medications. Therefore, there is an urgent need for new, safe, and effective compounds to combat antimicrobial resistance. The aim of this study was to synthesize new compounds derived from 2-hydroxy-1,2-diphenylethanone using the Mannich reaction and evaluate their antimicrobial activities against 26 bacterial strains and 4 fungal strains. Three compounds were successfully synthesized and their structures were confirmed as 2-hydroxy-1,2-diphenyl-3-(piperidin-1-yl)propan-1-one ( 2 ), 1-(2-hydroxy-3-oxo-2,3-diphenylpropyl)urea (3), and 3-(diethylamino)-2-hydroxy-1,2-diphenylpropan-1-one (4) using  ¹H and ¹³C-NMR spectroscopy. All the synthesized compounds exhibited broad-spectrum antibacterial activity. Compound ( 3) demonstrated the highest activity, with MIC of 10 µg/mL against Shigella sonnei 1, Shigella boydii D13629, and Pseudomonas aeruginosa MDR1 and compound ( 4) demonstrated the highest antifungal activity, with MIC of 200 µg/mL against Candida albicans ATCC 10231, Aspergillus niger ATCC 6275, Penicillium funiculosum NCTC 287, and Penicillium notatum ATCC 11625. Molecular docking showed the compounds interact favorably with conserved residues in the binding site of E. coli DsbA (PDB ID: 8DN0) through hydrogen bonding and hydrophobic interactions, with docking scores of –7.5 kcal/mol compound (3) , –7.1 kcal/mol compound (4) , and –6.5kcal/mol compound (2) . This research suggests verify the molecular docking results experimentally and biological activities, such as antiviral, anticancer, anti-inflammatory, and antioxidant properties and evaluate the safety profile of the produced chemicals, conduct thorough toxicity tests.