Promising bio-active complexes of divalent metal ions of 2-thiouracil: Synthesis, antibacterial, anticancer, molecular docking, and study the nano structures

The study reports the synthesis, characterization and biological evaluation of ten divalent metal complexes derived from 2-thiouracil (HTU). The study reports the synthesis, characterization and biological evaluation of ten divalent metal complexes derived from 2-thiouracil. The complexes were characterized by different technique methods. The IR data reveal different coordination modes: bidentate chelation thru carbonyl-O and ring-N or thiocarbonyl-S and ring-N, depending on the metal center. The formation of crystalline nanoscale aggregates with particle size ranging from 53 to 112 nm was confirmed by X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) and was influenced by the metal ions involved. The antibacterial activity was studied against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis and most of the complexes showed better activity than free ligand, especially platinum (II) complex [Pt(TU) 2 ] (TU − : 2-thiouracilate; deprotonated form)exhibited excellent activity index (79–84%) followed by Zn(II) complex. The anticancer activity of some selected complexes (Ni, Zn, Pd, Pt) against human liver cancer cell line (HepG2) was evaluated by MTT assay. The results showed a significant dose dependent cytotoxicity by Pt(II) (55.8%) and Zn(II) (48.1%) complexes at 500 μg/mL. Further, a docking study assessing coordination complexes for HDAC2 binding, various compounds were compared to the reference ligand KRU (affinity: −6.50 kcal/mol). Compound 3 (−6.10 kcal/mol) was still able to interact with the Zn 2+ , but it presented fewer contacts with Asp/His residues. Compounds 6 (−7.17 kcal/mol) and 8 (−7.05 kcal/mol) showed a better occupancy of the pocket; compound 6 coordinated the Zn 2+ and interacted with several residues, while compound 8 chelated the Zn 2+ and established strong hydrogen bonds with key residues of the active site.