الفهرس | Only 14 pages are availabe for public view |
Abstract In liver research laboratory (FAB-Lab, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt), Prof. Dr. Farid Badria and his research team initiated a series of studies for better utilization of natural products and their semi-synthetic derivatives as potential therapeutic agents including enzyme inhibitors. All of the previous examples are about using single compound that targets one enzyme (on-target approach), with high selectivity. In parallel, it was found that molecules hitting more than one target may have in principle a safer profile compared to single-targeted ones. Therefore, promiscuous (multi-target) enzyme inhibitors are the major objectives of this study. Part I. General biological screening of selected medicinal plant extracts against three metabolic enzymes (alpha amylase, tyrosinase and hyaluronidase). Phyllanthus emblica leaves extract exerted the highest inhibitory effect against α-amylase with (98.37 % inhibition), a good tyrosinase inhibitory activity with 52.84 % inhibition, hyaluronidase with 115.77 % inhibition. Part II: Bio-guided fractionation of Phyllanthus emblica extract, isolation, purification and structural elucidation of compounds with enzyme inhibitory activity. The ethyl acetate fraction of Indian gooseberry was found to be the most active one. Against the three enzymes with high antioxidant and polyphenolics potential. It was subjected to further fractionation and purification to afford for compounds which were identified as luteolin-7-O-α-L-rhamnoside, apigenin7-O-α-L-rhamnoside, methyl gallate and gallic acid. Part III: Biological, virtual screening and in silico molecular properties (ADMET and drug-likeness prediction). luteolin-7-O-α-L-rhamnoside was found to be the compound responsible for the enzyme inhibitory activity against alpha amylase, tyrosinase and hyaluronidase. |