Design, synthesis, insilco docking and biological evaluation of new 5-oxo-imidazoline derivatives as potent polo– like kinase 1 inhibitors

This study involved the synthesis of novel 4-Benzylidene-1-(5-sulfonyl-1,3,4-oxadiazol-2yl)-5-oxo-imidazoline derivatives (4a-4j) with satisfactory to outstanding yield. These compounds were then subjected to in silico experiments to evaluate their effectiveness against the polo-like kinase1 enzyme. The structures were analysed utilising spectroscopic techniques including 1H-NMR, 13C-NMR, and LC/MS. Extensive computational analyses were conducted, which involved evaluating the drug-likeness and ADMET characteristics, as well as performing molecular docking and molecular dynamics (MD) simulation investigations. The newly created analogues of the unique compound were subjected to docking analysis using Polo-Like Kinase 1 (PDB 2RKU) enzymes to study their binding interactions. Due to its exceptionally low binding affinity for Polo-Like Kinase 1. An MD simulation investigation demonstrated consistent and enduring binding throughout the whole simulation. All the substances have undergone testing in conjunction with the medication Tamoxifen. The compounds containing 3-hydroxy-4-methoxy (4h) and 4-hydroxy (4d) substitutions were shown to have notable cytotoxic effects. All the results yield crucial data for subsequent chemical experiments. Therefore, this study provides fundamental insights and valuable data necessary for subsequent chemical experiments besides drug development efforts. The promising activity of specific derivatives against Plk1, combined with their notable cytotoxic effects, suggests their potential for further exploration in the context of cancer therapeutics. These outcomes could have the way for developing new treatments targeting specific pathways involved in cancer progression.