Design, synthesis, and in-vitro evaluation of β-(Thiosemicarbazide/Thiosemicarbazone)-Sulfides targeting Klebsiella pneumoniae : exploring binding interactions with topoisomerase IV and KPC-2 carbapenemase via molecular docking

A novel series of β-(thiosemicarbazide/thiosemicarbazone)-sulfide derivatives (6a – i and 8a – k) was synthesized through a streamlined multi-step approach designed to yield new antibacterial candidates. Structural elucidation was accomplished using comprehensive spectroscopic techniques. The antibacterial efficacy of the synthesized compounds was evaluated via minimum inhibitory concentration (MIC) assays against multiple bacterial strains. Notably, compounds 6d, 6e, and 6 h demonstrated potent and selective activity against Klebsiella pneumoniae (K. pneumoniae) with MIC values of 50 µg/mL, compared to the reference drug ciprofloxacin (MIC ≥ 32 µg/mL). These compounds also exhibited significant antioxidant activity in DPPH radical scavenging assays, with inhibition ranging from 75.13% to 83.74%, approaching that of ascorbic acid (87.5%). Molecular docking studies further supported their potential, revealing stable binding interactions with the active sites of K. pneumoniae topoisomerase IV and carbapenemase enzymes. Collectively, these findings highlight the dual antibacterial and antioxidant potential of the synthesized derivatives, positioning them as promising candidates for further development, particularly against multidrug-resistant K. pneumoniae.