Synthesis, characterization and evaluation of antioxidant and antibacterial activities of novel isatin-derived hydrazone derivatives of N-amino-11-azaartemisinin

The rise of antibiotic-resistant bacterial infections and the associated oxidative stress highlight the urgent need for new therapeutic agents. Artemisinin 1 and isatins are both pharmacologically active compounds with significant antibacterial, antimalarial, anticancer, and antioxidant properties respectively. In this study, we synthesized and biologically evaluated a series of isatin-derived hydrazones 14a-z of N-amino-11-azaartemisinin, aiming to address gaps in the development of effective drugs for oxidative stress and bacterial infections. The antioxidant activity was assessed through the DPPH radical scavenging assay, revealing compound 14a (IC₅₀ = 1.54 ± 0.53 μg mL⁻¹) as highly potent, comparable to L-ascorbic acid (IC₅₀ = 1.60 ± 0.62 μg mL⁻¹). Notably, antibacterial tests highlighted compound 14o as having superior efficacy (MIC = 0.25 μg mL⁻¹) against E. coli, while 14l exhibited excellent activity (MIC = 0.5 μg mL⁻¹) against Bacillus subtilis. In addition to these biological evaluations, we explored the thermodynamic properties of synthesised compounds using isothermal titration calorimetry (ITC) and studied the thermal stability and degradation patterns through thermogravimetric analysis (TGA). These findings underscore the potential of isatin-derived hydrazones as novel drug candidates for combating bacterial infections and free-radical associated conditions, contributing to the ongoing search for innovative therapies in the face of growing resistance and global health challenges.