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

Abstract The pressing demand for novel antibiotics to counter drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (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 in vitro against a range of pathogens, including fungi like Aspergillus fumigatus (RCMB 002008), Gram-negative bacteria like Escherichia coli (ATCC 25922), and Gram-positive bacteria like Staphylococcus aureus (ATCC 25923) and MRSA (USA300). Notably, the thieno-thiazolo-quinazoline compounds 4 and 5 demonstrated a strong ability to inhibit and disrupt MRSA USA300 biofilm formation across all tested concentrations. Furthermore, in an in vivo 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.