Five, six and/or seven-membered rings endowed with isoxazole moiety: synthesis, antimicrobial assessment and in silico molecular docking studies

Aims The incorporation of isoxazole structural elements into pharmaceutical compounds reflects ongoing efforts by researchers to explore the therapeutic potential associated with this distinctive chemical motif. Owing to its notable reactivity and versatile synthetic potential, 3-phenylisoxazol-5(4H)-one 2 was selected as a key starting material for the synthesis of a series of novel isoxazole and/or fused isoxazole derivatives 3–13.Materials and methods Their chemical structures were confirmed utilizing various spectroscopic techniques. Additionally, the newly compounds were screened for antimicrobial activities. Furthermore, docking studies were performed against the enzymes E. coli rhomboid protease (PDB ID 3ZMI) and trichodiene synthase from Fusarium (PDB ID 2PS6), using ampicillin and clotrimazole as antibacterial and antifungal standard drugs, respectively. Structure activity relationship (SAR) for compound 11 was rationalized by investigating the effect of substituents on inhibitory potential.Results Among them, compound 11 demonsrated the strongest antibacterial and antifungal potency with minimum inhibitory concentration (MIC) value (15 µg/mL), comparable to ampicillin and clotrimazole, respectively; making it as a most promising candidate. In the same manner, it also declared the best binding energies comparable to standards.Conclusions Our work recommends that 11 could be promising lead for development of potent antimicrobial drug candidates.