Thirty-two new naphthylthiazole derivatives were synthesized with the aim of exploring their antimicrobial effect on multidrug-resistant Gram-positive bacteria. Compounds 25 and 32, with ethylenediamine and methylguanidine side chains, represent the most promising derivatives, as their antibacterial spectrum includes activity against multidrug-resistant staphylococcal and enterococcal strains. Moreover, the new derivatives are highly advantageous over the existing frontline therapeutics for the treatment of multidrug-resistant Gram-positive bacteria. In this vein, compound 25 possesses three attributes: no bacterial resistance was developed against it even after 15 passages, it was very efficient in targeting intracellular pathogens, and it exhibited a concentration-dependent ability to disrupt the preformed bacterial biofilm.
Keywords: MRSA biofilm; antibiotic resistance; intracellular bacteria clearance; prolonged half-life; vancomycin-resistant Staphylococcus aureus.