Authors: Mohit M. Jain; Nirmala Kumari; Geeta Rai
Addresses: Neiss Wellness India Limited, Mumbai 400064, India ' Neiss Wellness India Limited, Mumbai 400064, India ' Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221005, India
Abstract: LXR (encoded by NR1H2 and 3) and FXR (known as bile acid receptor) encoded by NR1H4 (nuclear receptor subfamily 1, group H and member 4) are nuclear receptors in humans and are important regulators of bile acid production, cholesterol, fatty acid and glucose homeostasis hence responsible for liver detoxification. Several strategies for drug design with numerous ligands for this target have failed owing to the inability of the ligand to access the target/receptor or their early metabolisation. In this work, we have evaluated FXR and LXR structure bound with agonist and compared the binding energy affinity of active ligands present in live green-real veggies with reference drugs (ligands) present in the market. A high throughput screening combined with molecular docking, absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions, log P values and percentage of human oral absorption value led to the identification of two compounds present in live green-real veggies with strong potential for liver detoxification.
Keywords: FXR; bile acid receptors; LXR; liver detoxification; veggies; glutathione; glucosinolate; indole-3-carbinol; in-silico studies; green vegetables; nuclear receptors; bile acid production; cholesterol; fatty acid; glucose homeostasis; drug design; agonist; binding energy; active ligands; human oral absorption; molecular docking.
International Journal of Computational Biology and Drug Design, 2015 Vol.8 No.1, pp.75 - 86
Accepted: 02 Dec 2014
Published online: 07 Apr 2015 *