1,2-Benzothiazine derivatives: antibacterial and antifungal activity with structure-activity relationship insights

The rise of multidrug-resistant bacteria presents a major global health challenge, driving the search for novel antibacterial agents. 1,2-Benzothiazine derivatives have emerged as versatile scaffolds with potential to overcome bacterial resistance. This review analyses studies from 2000 to 2025 on bicyclic, tricyclic, arylpiperazine, and metal-complexed 1,2-benzothiazines, highlighting their antibacterial and antifungal activities. Most bicyclic and tricyclic derivatives exhibited limited efficacy, whereas tricyclic pyrazole-substituted compounds targeting the NorA efflux pump, particularly 12i, effectively restored ciprofloxacin activity against Staphylococcus aureus and inhibited biofilm formation. Arylpiperazine derivatives demonstrated potent bactericidal activity against both Gram-positive and Gram-negative bacteria, surpassing reference antiseptics, while copper(II) complexes enhanced antibacterial potency. Antifungal activity was generally weak, limited to select hydrazide derivatives. Overall, NorA inhibitors and arylpiperazine 1,2-benzothiazines represent promising leads for the development of next-generation antibacterial agents and adjuncts to antibiotic therapy.