Advances in In-silico based Predictive In-Vivo Profiling of Novel Potent β- Glucuronidase Inhibitors
[ Vol. 19 , Issue. ]
Maria Yousuf*Pages 1-14 (14)
Background: Intestinal β-glucuronidase enzyme has significant importance in colorectal carcinogenesis. Specific inhibition of the enzyme helps to prevent immune reactivation of the glucuronide-carcinogens thus, protects the intestine from ROS (Reactive Oxidative Species) mediatedcarcinogenesis. Objectives:Advancements to the In-silico based techniques is providing broad range of studies to facilitate the drug designing and development process speedily through SwissADME and BOIELD-Eggtools. Methods: In our designed case of study we used SwissADME and BOIELD-Egg predictive computational tools to estimate the physicochemical, human pharmacokinetics, drug-likeness, medicinal chemistry properties and membrane permeability characteristics of our recently In-vitroevaluatednovelβ-Glucuronidaseinhibitors. Results: Out of the eleven screened potent inhibitors, compound (8) exhibited the excellent bioavailability radar against the six molecular descriptors, good absorption, distribution, metabolism and excretion properties along with P-glycoprotein, CYP450 isozymes and membranes permeability profile, on the basis of these factual observations compound (8) can be predict to get in-vivio experimental clearance efficiently, Therefore in future it can be a drug in market, to treat the various disorders associated with the over expression of β-Glucuronidase, enzyme including various types of cancers, particularly hormone-dependent cancers such as (breast, prostate, and colon cancer), while other compounds (1-7, & 9-11), are also showing good predictive pharmacokinetics, medicinal chemistry , BBB and HIA membranes permeability profiles with the requirement of slight lead optimization to get the improved and enhance results. Conclusion: In the consequence in-silico based studies are considered to provide robustness towards a rational drug design and development approach hence to avoid the possibility of failures of drug candidates in the later stages of drug development phases. The results of this study smartly reveal the possible attributes of potent β-Glucuronidase inhibitors, for further experimental evaluation.
β-Glucuronidase enzyme, Colorectal carcinogenesis, SwissADME, BOIELD-Egg, Pharmacokinetics, Druglikeness, Blood Brain Barrier (BBB), Human intestinal absorption (HIA)
Dow College of Biotechnology, Department of Bioinformatics, Dow University of Health Sciences Karachi
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