Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates

Functionalized isoxazoles provide valuable structural motifs, opening up a wide range of uses in the medicinal, pharmacological, and pharmaceutical fields. Within this scope, an efficient approach has been adopted to synthesize a novel series of functionalized isoxazole derivatives, starting from aza-aurone, providing reproducible access to the desired isoxazoles in excellent yields. All synthesized compounds were structurally elucidated through the use of various spectroscopic techniques and mass spectrometry. The derivatives generated were screened for their antimicrobial potential against the fungus Candida albicans as well as three bacterial strains. The results show that almost all of the tested isoxazole derivatives were found to be significantly potent against the fungus C. albicans. The functionalized isoxazoles were also computed using the Gaussian software package with the 6-31++G(d,p) basis set at B3LYP, HF, and M062X levels, and their chemical activities were compared. Moreover, the molecular docking studies of tested isoxazole compounds were performed against the C. albicans receptor. The results suggest that the newly synthesized compounds exhibit docking scores ranging from -10.29 to -15.08 kcal/mol, revealing a high affinity for the target enzyme (5V5Z). Lastly, drug similarity studies and ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties assessments indicate that isoxazole derivatives have favorable absorption, distribution, and metabolism properties associated with a proven lack of toxicity.