Exploration of Antituberculosis Potential of Ni(II) and Zn(II) Serine-Tyrosine Dithiocarbamate Complexes: Synthesis, Characterization, In Silico Profile, and In Vitro Evaluation

Abstract

Tuberculosis (TB) remains a global health challenge, with millions of new cases and deaths reported each year. The emergence of drug resistance and treatment side effects has driven the development of new therapeutic agents, including the use of dithiocarbamate metal complex compounds. This study aims to synthesize and characterize Ni(II) and Zn(II) complexes with serine-tyrosine dithiocarbamate ligands and evaluate their antituberculosis bioactivity. The method in this study involves the synthesis and characterization of Ni(II) and Zn(II) complexes with serine-tyrosine dithiocarbamate, including melting point determination, conductivity measurement, and spectroscopic analyses (UV-Vis, FT-IR, XRD, and SEM-EDS). Furthermore, the bioactivity of the synthesized metal complexes was evaluated using both in silico approaches (Lipinski's rule of 5, ADMET profiling, and molecular docking) and in vitro testing using the Lowenstein-Jensen method. The synthesis and characterization results show that the successfully synthesized metal complexes are solid, non-electrolyte, stable, and have typical characteristics of dithiocarbamate complexes. In silico analysis shows compliance with Lipinski’s rule and most ADMET parameters, indicating potential as oral drug candidates. Molecular docking revealed strong interactions, particularly for the Ni(II)Ser-Tyr Dtc complex with the highest binding score ( 95.0923 kJ/mol), exceeding INH ( 65.8232 kJ/mol). In vitro results confirmed antibacterial activity by the absence of M. tuberculosis H37Rv colony growth. These findings suggest the metal complexes have potential as antituberculosis agents. HIGHLIGHTS Ni(II) and Zn(II) metal complexes with serine-tyrosine dithiocarbamate ligands were successfully synthesized and characterized (UV-Vis, FT-IR, XRD, SEM-EDS). The metal complexes met Lipinski’s rule and most ADMET criteria, with Ni(II)Ser-Tyr Dtc showing the strongest binding to Enoyl-ACP reductase, outperforming isoniazid. In vitro assays confirmed antituberculosis activity, indicated by the absence of tuberculosis H37Rv colony growth. The results highlight the potential of these metal complexes as promising antituberculosis drug candidates. GRAPHICAL ABSTRACT

Access to Document

Other files and links

• Link to publication in Scopus
• Open Access Version Available

Fingerprint