Unlocking the biological potential of transition metal complexes with Thiosemicarbazone ligands: Insights from computational studies

• Published in: Heliyon Vol. 10; no. 12; p. e33150
• Main Authors: Khurana, Daksh, Kumar, Binesh, Devi, Jai, Antil, Nidhi, Patil, Rajesh B., Singh, Khushwant, Singh, Yudhvir
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 30.06.2024; Elsevier
• Subjects: ADMET; Anti-tuberculosis; Anticancer; Molecular docking; Transition metal; Transition metal; Anticancer; Anti-tuberculosis; ADMET; Molecular docking
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e33150

In the previous study, the synthesis and characterization of 4-(3-fluorophenyl)-3-thiosemicarbazide and benzaldehyde derivatives based thiosemicarbazone ligands and their Co(II), Ni(II), Cu(II), Zn(II) complexes were carried out to evaluate their malarial and oxidant and inflammatory inhibition abilities, demonstrating that these compounds have robust efficacy for these ailments. In the present research, to find out a combating agent against breast cancer, tuberculosis, bacterial and fungal ailments, the compounds were tested through MTT, microplate alamar blue and serial dilution protocols. ADMET and DFT investigation were analyzed against highly bioactive compounds (2, 7–10) to give a new insight about compound's reactivity, stability and drug likeness properties. Furthermore, activity results shows that the ligand (2) and its complexes demonstrate greater efficacy compared to ligand (1) and its complexes. The Cu(II) (9) and Zn(II) (10) complexes were observed as highly efficient for breast cancer (MCF-7 cell line), TB (H37Rv strain), bacterial and fungal ailments in comparison of standard drugs with 0.029 ± 0.001 μM IC50 value for (9) in anticancer activity and 0.0034 ± 0.0017 μmol/mL MIC value for (10) in anti-tuberculosis activity. In the molecular docking investigation, the various kind of binding interactions and lowest binding affinity of (9) (against 4RJ3 (−10.0 kcal/mol), 2VCJ (−7.9 kcal/mol)) and (10) (−7.8 and −8.3 kcal/mol for 5V3Y and 3PTY protein) support their bioactivity. This research highlights the pharmaceutical importance of transition metal complexes having thiosemicarbazones, presenting a significant approach for the discovery of potent anti-infectious agent. •Investigation of anticancer, anti-TB, antibacterial and antifungal potential of the compounds.•The compounds (1-10) were found as significantly potent.•Complexes (9, 10) shows highest activity for cancer, TB, bacterial and fungal deformities.•Molecular docking, ADMET and DFT studies supports biological results.