New thiazolyl-isoxazole derivatives as potential anti-infective agents: design, synthesis, and antimicrobial efficacy.

Antimicrobial resistance threatens the efficacious prevention and treatment of infectious diseases caused by microorganisms. To combat microbial infections, the need for new drug candidates is essential. In this context, the design, synthesis, antimicrobial screening, and study of a new series of 5-aryl-3-(2-arylthiazol-4-yl)isoxazole () have been reported. The structure of new compounds was confirmed by spectrometric methods. Compounds were evaluated for antitubercular and antimicrobial activity. Against H37Rv, fourteen compounds showed good to excellent antitubercular activity with MIC 2.01-9.80 µM. Compounds , and showed four-fold more activity than the reference drug isoniazid. Nine compounds, , , , , , , , , showed good antibacterial activity against with MIC 7.8-15.62 µg/mL. Against , four compounds showed good activity with MIC 31.25 µg/mL. Against , all twenty compounds reported excellent to good activity with MIC 7.8-31.25 µg/mL. Compounds , , and showed comparable activity concerning the reference drug fluconazole. The compounds were screened for cytotoxicity against 3t3l1 cell lines and found to be less or non-cytotoxic. The study exposed that these compounds displayed high affinity towards the targets PanK, DprE1, DHFR, PknA, KasA, and Pks13, and targets NMT, CYP51, and CS. The compound was evaluated for structural dynamics and molecular dynamics simulations. The potent antitubercular and antimicrobial activity of 5-aryl-3-(2-arylthiazol-4-yl)isoxazole ( derivatives has recommended that these compounds could assist in treating microbial infections.Communicated by Ramaswamy H. Sarma.