Synthesis of Novel Pyrazole–Oxazolidine Hybrids and Their In Vitro Antimicrobial Evaluation and In Silico Molecular Docking

Abstract

A series of novel pyrazole–oxazolidine–morpholine hybrids―4-[4-(5-{[1-phenyl-3-(R-phenyl)-1H-pyrazol-4-yl]methyleneamino}methyl)-2-oxo-oxazolidin-3-yl)phenyl]morpholin-3-ones―were synthesized via the Vilsmeier–Haack reaction and screened for antimicrobial activity against Gram+ve (S. aureus, S. pyrogens) and Gram–ve (E. coli, P. aeruginosa) bacterial and fungal (C. albicans, A. clavatus, and A. niger) strains. All the products showed moderate antimicrobial activities, with the largest zones of inhibition showed by the derivatives with R = 3-Br and 4-Me. Molecular docking of the synthesized hybrids against a series of bacterial (PDB ID: 1JIJ, PDB ID: 4ROT, PDB ID: 1KZN, and PDB ID: 4JVI) and fungal (PDB ID: 5C5G, PDB ID: 1IYL, PDB ID: 1UKC) protein targets to assess their inhibitory potential. The results predicted that (E)-4-[4-(5-{[3-(bromophenyl)-1-phenyl-1H-pyrazol-4-yl]methyleneamino}methyl)-2-oxo-oxazolidin-3-yl)phenyl]morpholin-3-one and its 3-(4-methylphenyl) analog may exhibit antimicrobial activity and deserve further study as promising candidates for medical applications.