In vitro pharmacological, in vivo toxicological and in silico molecular docking analysis of glycopentalone, a novel compound from Glycosmis pentaphylla (Retz.) Correa

Hepatocellular carcinoma or liver cancer is recognized as an intricate, multifactorial disease originates from hepatocytes so it is called hepatocellular cancer or carcinoma. Chronic infection with hepatitis B virus, hepatitis C virus and alcoholism are the major factors contributing to the development of hepatocellular carcinoma. Glycopentalone is a novel anti-hepatocellular carcinoma compound isolated from Glycosmis pentaphylla (Retz.) Correa. The present work focused to identify the effect of glycopentalone on major hepatic residents like macrophages, stellate cells, and hepatocellular carcinoma cells, by in vitro methods and also to evaluate its kinase inhibitory effect by in silico approaches. IC50 concentration of glycopentalone and other standard chemotherapeutics were compared by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle regulatory effect of sorafenib and glycopentalone was documented by fluorescence activated cell sorting analysis. Anti-fibrotic, anti-inflammatory, and anti-metastatic effect of glycopentalone was evaluated using Reverse Transcription Polymerase Chain Reaction by quantifying the mRNA level expression of selected gene associated with it. Kinase inhibitory effect of sorafenib and glycopentalone was confirmed using ArgusLab docking software. In vivo acute toxicity studies were done on Wistar rat animal models. The in vitro biological activity studies showed that glycopentalone has significant anti-inflammatory, anti-metastatic, and anti-fibrotic activities. In silico molecular docking of glycopentalone point out that it has potential anti-kinase activity, compared to the standard drug sorafenib. In vivo toxicity studies proved that glycopentalone did not cause significant toxicity associated morphological, biochemical, and histopathological changes on rat liver. Therefore, after the detailed in vivo case model studies, glycopentalone can be used for formulation of drugs or can be used as intermediates for new semi-synthetic drug for the preparation of standardized galenicals.