Design, synthesis, biological assessment and molecular docking studies of some new 2-Thioxo-2,3-dihydropyrimidin-4(1H )-ones as potential anticancer and antibacterial agents

In this study, a series of thiouracil derivatives were designed and synthesized based on conventional approach and pharmacophoric features essential for TS inhibitors. The chemical structures of all synthesized compounds were elucidated by various techniques ranging from micro-elemental analyses to spectral analyses. The new thiouracil derivatives were evaluated for their anticancer and antibacterial activities. All the new synthesized compounds were evaluated in vitro against MCF-7 cell line. The anticancer results displayed that compounds 8, 11, 13a , and 12 , exhibit the highly significant effect against breast cancer cell line with IC50 values of 3.80, 4.00, 4.50, and 4.70 mu g/ml, respectively compared with doxorubicin. Furthermore, molecular docking studies were performed to suggest possible mechanism of action of the designed compounds and explain the anti-breast cancer results with prospective target, thymidylate synthase (PDB:1JU6). On the other hand, the antibacterial activity of the new compounds was screened against three significant representative strains including Escherichia coli, and Pseudomonas aeruginosa as gram negative bacterium and Staphylococcus aureus as gram positive bacterium using agar well diffusion method. The antibacterial activity results revealed that most of the tested compounds exhibited significant antibacterial activity. In particularly, compounds 13a , and 13b were found to be the most potent antibacterial agent with inhibition zone values of 38 and 35 mm at the concentration of 50 mu g/ml against Escherichia coli, and inhibition zone values of 25 and 23 mm at the concentration of 50 mu g/ml against Staphylococcus aureus. However, all tested strains showed resistance to synthesized compounds except, compound 7 which exhibited significant activity only against Pseudomonas aeruginosa with inhibition zone values of 22 mm at the concentration of 50 mu g/ml. Further, molecular docking investigation was carried out to gain insight into the binding mode of the most promising compounds using crystal structure of S. aureus DNA gyrase complex with ciprofloxacin (PDB ID: 2XCT). (c) 2020 Elsevier B.V. All rights reserved.