Synthesis, Spectroscopic Characterization and In-Vitro Antimicrobial Evaluation of New Hydrazide-Functionalized Carbazole Derivatives

The escalating global crisis of antimicrobial resistance (AMR) necessitates the urgent development of novel therapeutic agents. Carbazole, a privileged scaffold in medicinal chemistry, is known for its diverse biological activities. This study aimed to synthesize and characterize novel carbazole-based hydrazide derivatives and evaluate their antibacterial potential. Two target compounds, 2-(2-chloro-9H-carbazol-9-yl) acetohydrazide (IIIa) and 2-(3-bromo-9H-carbazol-9-yl) acetohydrazide (IIIb), were synthesized via a two-step procedure involving N-alkylation of substituted carbazoles with ethyl chloroacetate, followed by hydrazinolysis. The structures of the synthesized compounds were unequivocally confirmed using sophisticated spectroscopic techniques, including FTIR and ¹H NMR. The compounds were obtained in good yields (68-76%) and exhibited sharp melting points, indicating high purity. In-vitro antibacterial screening against Staphylococcus aureus (Gram-positive) and Pseudomonas aeruginosa (Gram-negative) strains revealed promising activity. Compound IIIa (Cl-substituted) showed superior potency with Minimum Inhibitory Concentration (MIC) values of 12μg/mL and 9μg/mL, respectively, compared to IIIb (Br-substituted) with MICs of 18μg/mL and 16μg/mL. The results establish a preliminary structure-activity relationship, indicating that the nature and position of the halogen substituent significantly influence antibacterial efficacy. These findings position these novel carbazole hydrazides as promising lead compounds for the development of new antimicrobial agents to combat drug-resistant bacteria.