Design, Characterization, Antimicrobial Activity, and <i>In Silico</i> Studies of Theinothiazoloquinazoline Derivatives Bearing Thiazinone, Tetrazole, and Triazole Moieties

The pressing demand for novel antibiotics to counter drug-resistant bacteria, such as methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), underscores the serious public health threat posed by antibiotic resistance. To address this issue, novel quinazoline-4-one derivatives were developed, synthesized, and evaluated <i>in vitro</i> against a range of pathogens, including fungi like <i>Aspergillus fumigatus</i> (RCMB 002008), Gram-negative bacteria like <i>Escherichia coli</i> (ATCC 25922), and Gram-positive bacteria like <i>Staphylococcus aureus</i> (ATCC 25923) and MRSA (USA300). Notably, the thieno-thiazolo-quinazoline compounds <b>4</b> and <b>5</b> demonstrated a strong ability to inhibit and disrupt MRSA USA300 biofilm formation across all tested concentrations. Furthermore, in an <i>in vivo</i> MRSA skin infection model, these compounds effectively reduced bacterial counts compared to both vehicle-treated and untreated control groups. To enhance understanding and provide deeper insights, ADMET and docking simulations were also conducted.