Copper(II) and zinc(II) complexes of N2O2-thiosemicarbazones as inhibitors of Mycobacterium tuberculosis and bacterial quorum sensing

The rise of resistance to existing antimicrobial drugs has become a significant global health concern, underscoring the urgent need for new and effective antimicrobial agents. In this context, we prepared six copper(II) (Cu1-Cu6) and six zinc(II) (Zn1-Zn6) complexes bearing N2O2-thiosemicarbazones and confirmed their structures by spectral techniques, including X-ray diffraction analysis. The antimicrobial potential of the target compounds was initially tested against drug-sensitive and isoniazid-resistant Mycobacterium tuberculosis strains. Cu(II)-based complexes were identified as more effective antitubercular agents with negligible cytotoxicity compared to Zn(II)-including counterparts. Furthermore, Cu1-Cu6 and Zn1-Zn6 were tested for their antibacterial and antifungal properties. Although the compounds failed to inhibit the growth of bacterial and fungal strains at low concentrations, Zn1 and Zn2 were determined as effective blockers of the bacterial cell-to-cell communication system known as quorum sensing. Finally, molecular docking studies indicated that inhibiting the enoyl acyl carrier protein reductase (InhA) enzyme could be the mechanism behind the significant antitubercular activity of Cu2. Overall, our study shows that copper(II) and zinc(II) complexes of thiosemicarbazones are promising agents against bacterial infections due to their antitubercular and anti-quorum sensing activities.