Platinum(II) Complexes of 3-Hydroxypyridine-2-carboxaldehyde, N(4)-Methyl and N(4)-Pyrrolidinyl Thiosemicarbazones: Synthesis, Characterization, and Primary Anticancer Screening Against HeLa Cells, and Molecular Docking

Background: Thiosemicarbazones are an important class of synthetic organic compounds exhibiting promising biological activities; antiviral, antibacterial, antitubercular, antiprotozoal, antimalarial, antifungal, enzyme inhibitory and antitumor. Different α-(N)-heterocyclic thiosemicarbazones are potent inhibitor of ribonucleotide reductase enzyme that play a critical role in DNA synthesis, moreover some have been found 1000-fold more potent than the clinical drug hydroxyl urea. Objective: Different coordination complexes have been assessed for their efficacy to target MDR and surpass side effects associated with platinum drugs. In this work, we have prepared and investigated the anticancer potential of new platinum compounds of 3- hydroxy-2-formylpyridine thiosemicarbazones. Methods: Novel Pt(II) complexes, were synthesized and characterized by elemental analyses, FT-IR, 1H-NMR, UV-Visible spectroscopy and mass spectrometry. The in vitro anticancer activity of the synthesized compounds against HeLa cells by MTT assay was assessed. Protein-fixed and ligand-flexible Docking studies were carried out using Lamarckian genetic algorithm and Auto dock 4.2 software. Results: The IC50 values of compounds (3) and (4) through MTT screening against HeLa cells were found 107.16 µM and 132.13 µM respectively. The binding energy value for the complex [Pt(HyPyMe)Cl] was -6.49 kcal/mol. While for complex, [Pt(HyPyPyrd)Cl] was found to have a binding energy value of -6.83 kcal/mol. Conclusion: The spectroscopic and analytical data showed the mononuclear structures and square planar geometry of the Pt(II) complexes. The compounds exhibited moderate antineoplastic activity and N(4)-methyl substituted compound exhibited better anticancer activity. [Pt(HyPyMe)Cl] complex forms Hydrogen bond interactions with guanine-6, guanine-7 and thiamne-8. While [Pt(HyPyPyrd)Cl] interacts with guanine-7 and guanine-16 via hydrogen bond interaction.