HEPATOPROTECTIVE PERSPECTIVE OF NEWLY SYNTHESIZED 3-(3,5-BIS (TRI FLUORO METHYL) PHENYL)-5-METHYL-1-((1-METHYL-1H-PYRROL-2-YL) METHYL)-2-THIOXOIMIDAZOLIDIN-4-ONE AGAINST DIETHYL NITROSAMINE INDUCED LIVER INJURY IN RATS WITH MOLECULAR DOCKING INVESTIGATION.

The hepatoprotective effect of synthesized 3-(3,5-bis (trifluoromethyl) phenyl)-5-methyl-1-((1- methyl-1H-pyrrol-2-yl) methyl)-2-thioxoimidazolidin-4-one (3FL-M) was evaluated against diethyl nitrosamineinduced liver injury (DEN). Wistar rats were divided into 3 groups as: placebo (received 10% tween 80%), hepatotoxic control (injected with 200 mg/kg of DEN) and treatment (injected 200 mg/kg of DEN and received 50 mg/kg oral feeding of the synthesized 3FL-M). Half the number of the rats were sacrificed on 2nd week of the experiment, whereas the other half were sacrificed after 6 weeks. Blood was collected to run liver biochemical analysis, and to evaluate pro-inflammatory cytokines tumor necrosis factor-alpha TNF-α and interleukine6 IL-6. Liver sections were used to detect nuclear protein ki-67 and hepatocyte specific antibody HSA. 3FL-M was subjected to molecular docking calculations based on binding affinities towards TNF-α and IL-6. DEN-treated rats showed elevation in the liver serum enzymes as well as pro-inflammatory cytokines with clear destruction of the hepatic architecture, in contrast 3FL-M treated rats showed normalized liver enzymes and cytokines levels with resolution of the hepatocytes. Molecular modelling revealed that 3FL-M exhibited the significant affinities toward the binding pocket of the TNF-α and IL-6, however, further studies is recommended for developing it as a chemotherapeutic drug-like molecule. [ABSTRACT FROM AUTHOR]