Exploring SB2OME and metal complexes as antibacterial agents: synthesis, characterization and molecular docking

A series of new substituted dithiocarbazate, S-benzyl-β-N-2-methoxybenzoyl dithiocarbazate (SB2OME), and its metal complexes have been successfully synthesised and characterised. SB2OME was synthesised via condensation of S-benzyldithiocarbazate (SBDTC) with 2-methoxybenzoyl chloride before complexing with various metal ions to yield a tridentate ONS Cu(II), Zn(II), Co(II), and Ni(II) complexes. All compounds underwent characterization via various physico-chemical analyses. Antibacterial activities of all the compounds were evaluated against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922). ADMET prediction was utilised to assess drug-likeness. The molecular docking was used against mutant and wild-type DNA gyrase B receptor E. coli (PDB:1AJ6 and 4WUB) to evaluate whether the bioactivities of the compounds are in correlation with the mechanism of DNA supercoiling. In-vitro analysis demonstrated that SB2OME and its metal complexes exhibit certain effectiveness against S. aureus and E. coli, and their potency, as measured by MIC values, is significantly inferior to that of well-established antibiotics. The ADMET prediction showed that SB2OME and its metal complexes possess favourable drug-likeness properties. From the molecular docking study, all the synthesised compounds prefer to bind with wild-type compared to the mutant DNA gyrase B. However, the absence of agreement between the binding energy and experimental results indicates that DNA gyrase B might not be the possible mechanism of action for the investigated compounds, as compared to their MIC values. Hence, this study concluded the necessity for structural modifications to enhance potency and effectiveness against pathogenic bacteria, alongside exploring additional computational methods to gain a deeper understanding of how newly synthesized compounds exert their mechanism of action.