Design, synthesis, biological evaluation and molecular modeling investigation of new N′-(2-Thiouracil-5-oyl) hydrazone derivatives as potential anti-breast cancer and anti-bacterial agents

A series of novel N'-(2-thiouracil-5-oyl)hydrazones were designed and chemically synthesized using an active substructure combination method. The synthesized compounds were structurally characterized on the basis of elemental (%) analyses, IR, MS, H-1 NMR, and C-13 NMR spectra. All the prepared compounds were evaluated in vitro against MCF-7 human breast cell line using MTT assay. The anticancer results showed that compounds 3j, 4a, 3c, 3b , and 3h exhibit the most prominent effect against breast cancer cell line with IC50 values of 3.40, 3.50, 3.60, 3.70, and 3.80 mu g/ml, respectively using doxorubicin as a control drug. Moreover, molecular docking studies were also performed in order to identify the binding mode mechanism of these compounds with prospective target, thymidylate synthase (PDB:1JU6). On the other hand, the antibacterial activities of all prepared compounds were screened in vitro against three bacterial strains, namely, Escherichia coli, and Pseudomonas aeruginosa as Gram negative bacteria and Staphylococcus aureus as a Gram positive bacterium using agar well diffusion method. The antibacterial activity results revealed that most of the compounds under test were inactive however, among all the tested compounds, only 3g and 4a , in a concentration of 50 mu g/ml showed a high antibacterial activity against the three used bacterial strained. It is worthy to note that the potency of 3g against Escherichia coli was comparable to that of the reference drug, while compound 2 exhibited significant activity against Pseudomonas aeruginosa only and compound 3j displayed low activity against Staphylococcus aureus. The structure-antibacterial activity relationship analysis can be modulated by the presence of aromatic or heteroaromatic moiety containing more lipophilic character significantly contributed to antibacterial activity. In addition, the drug-likeness properties have predicted for the target compounds. (C) 2021 Published by Elsevier B.V.