Efficacy of sulfamethoxazole metal complexes against resistant strains of mycobacterium tuberculosis: design, synthesis, characterization, and docking studies

<bold>Objective:</bold> In this study, we aimed to synthesize, dock, spectroscopically characterize, and assess the antimicrobial and mycobacterial efficacy of SMZ metal complexes. <bold>Methods:</bold> Six SMZ metal complexes were synthesized by reacting [4-amino-N-(5-methyl-1, 2-oxazol-3-yl) benzene sulfonamide] with metal salts of zinc (Zn), iron (Fe), silver (Ag), copper (Cu), cobalt (Co), and manganese (Mn). Antimicrobial activity against several resistant Gram-positive and Gram-negative pathogenic strains as well as against anti-mycobacterial resistant strains were evaluated. Finally, the synthesized metal complexes were docked into selected target proteins for M. tuberculosis, E. coli and S. aureus. <bold>Results:</bold> Prior to synthesis of SMZ metal complexes, the result of stoichiometric studies revealed the coordination of ligand to metal in the ratio of 2:1. SMZ-Mn complex (AZ106) showed highly significant activity against E. coli with MIC of 0.048µg/ml as well as against resistant pathogenic strains of tuberculosis, while almost all of the complexes showed significant antimicrobial activity against P. aeruginosa. On the other hand, SMZ-Ag complex (AZ103) showed highly significant activity against Gram-positive bacteria among all synthesized complexes. All of the synthesized SMZ complexes showed significant anti-mycobacterial activity than SMZ (standard). Moreover, docking algorithm of synthesized complexes proved them as promising antimicrobial and anti-mycobacterial agents with better binding affinities than reference drug (SMZ). <bold>Conclusion:</bold> SMZ metal complexes could serve as a therapeutic substitute in cases with MDR-TB.