New thiazolyl-isoxazole derivatives as potential anti-infective agents: design, synthesis,andantimicrobial 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, andstudy 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. Compoundswere evaluated forantitubercular and antimicrobial activity. AgainstH37Rv, fourteen compounds showed good to excellent antitubercular activity with MIC 2.01-9.80 µM. Compounds,andshowed four-fold more activity than the reference drug isoniazid. Nine compounds,,,,,,,,,showed good antibacterial activity againstwith 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,, andshowed comparable activity concerning the reference drug fluconazole. The compoundswere screened for cytotoxicity against 3t3l1 cell lines and found to be less or non-cytotoxic. Thestudy exposed that these compounds displayed high affinity towards thetargets PanK, DprE1, DHFR, PknA, KasA, and Pks13, andtargets NMT, CYP51, and CS. The compoundwas 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.