Synthesis, biological evaluation and molecular dynamics studies of oxadiazine derivatives as potential anti-hepatotoxic agents.

Generally, herbal medicines having remarkable popularity for treating liver ailments, but they are still unacceptable because of the deprivation of herbal drug standardization. Therefore, there is a need for promising synthetic drugs to overcome the critical liver problem. We introduce 1, 3, 4-oxadiazine ring in this study to identify better anti-hepatotoxic agents via a suitable synthetic route. These oxadiazine-based derivatives were structurally confirmed by analytical and spectral data and evaluated for their anti-hepatotoxic potential. Further, hepatotoxicity studies have been done to check the toxicity level in the synthesized compound. Compounds , , and were selected for further biological evaluation according to results. After that, CCl-induced animal model was used to evaluate anti-hepatotoxicity activity. Compound with 52.99%, 59.3%, 79.34% and with 52.16%, 57.65%, 75.10% revealed to be most promising for reduction in level of SGPT, SGOT and ALKP, respectively. Moreover, it was also observed that the compound with 411.01%, 53.39% and with 378.63%, 48.9% level of albumin and total protein were respectively. The induced-fit docking results of the compounds and reveal some essential binding information and exhibited desirable ADME properties, and obeyed Lipinski's rule of five. In addition, molecular dynamics studies for 100 ns further confirm the protein-ligand complex's stability, supporting the and data, and help in establishing the SAR of synthesized compounds. Two compounds, and , exhibited higher anti-hepatotoxic activity than the standard drug silymarin.