In silico evaluation of binding interaction and ADME study of new 1,3-diazetidin-2-one derivatives with high antiproliferative activity.

A series of eight novels' 1,3-diazetidin-2-ones have been proposed to assess their potential activities. They are intended to examine antiproliferative effects through inhibition of epidermal growth factor receptor (EGFR) expression. These eight compounds strongly interact with the EGFR protein, responsible for the activity. As part of a present study, these compounds were docked to the crystal structure of the EGFR (Protein Data Bank code: 1 M17) to determine their binding affinity at the active site. Based on computer predictions, two compounds were demonstrated high scores of 80.80 and 85.89. After analyzing ADME properties, these compounds were found to have significant potential for binding. Consequently, the abilities of gefitinib, erlotinib, imatinib, and sorafenib were selected for comparison as controls. Computational methods were performed to predict the critical disposition of eight novels' 1,3-diazetidin-2-one derivatives to the EGFR. Moreover, a docking technique employing the Genetic Optimization for Ligand Docking program was conducted. Compounds 2 and 7 demonstrate a high docking peace-wise scoring function (PLP) fitness of 85.89 and 80.80, respectively. They fulfilled the Lipinski's rule, topological descriptors, and fingerprints of drug-like molecular structure keys. These compounds can be used as lead compounds to develop novel antiproliferative agents. The outcome of applying this study is novel series of 1,3-diazetidin-2-one compounds as new analogs were designed and evaluated for their antiproliferative activity with a higher potency profile and binding affinity within the active sites of EGFR.