Open Access<i>In-silico</i> studies of HMG-Co A reductase inhibitors present in fruits of <i>Withania coagulans</i> Dunal (Solanaceae)
Author(s) -
Tooba Lateef,
Sadaf Naeem,
Shamim A. Qureshi
Publication year - 2020
Publication title -
tropical journal of pharmaceutical research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.209
H-Index - 36
eISSN - 1596-5996
pISSN - 1596-9827
DOI - 10.4314/tjpr.v19i2.13
Subject(s) - docking (animal) , hmg coa reductase , reductase , in silico , chemistry , active site , autodock , virtual screening , macromolecular docking , enzyme , biochemistry , protein data bank (rcsb pdb) , pharmacology , biology , medicine , drug discovery , gene , nursing
Purpose: To evaluate the antihypercholesterolemic effect of chemical constituents of W. coagulans by determining inhibitory effect of the compounds against HMG-CoA reductase, using in-silico methods.
Method: Docking simulations of twenty-one chemical constituents, found in the fruits of W. coagulans were performed against HMGCR(PDB ID: 2Q1L) using Molegro Virtual Docker software. The best docked poses were then selected, based on the docking score and amino acids involved in the interaction within the ligand and active site of protein.
Results: Five compounds viz. Coagulin D (comp no. 11), Ergosta-5,25-diene-3β,24ε-diol (comp no. 13), Withacoagulin (comp no. 15), and Withaferin (comp no. 16), showed the highest MolDock scores. These compounds with highest docking score, also formed hydrogen bond interactions with His (752), Lys (692, 735), Asp (690), Glu (559) within the binding site of HMG-CoA reductase, thus, halting enzyme activity. Whereas, Withanolide D (comp no. 17) with high MolDock score did not show hydrogen bonding interactions.
Conclusion: The high MolDock score and maximum binding with catalytic region of the enzyme indicate that compounds selected from the fruits of W. coagulans are potential blockers of HMG-CoA reductase. Thus, the compounds may be useful for the management of hypercholesterolemia, which untreated, often leads to coronary artery disease.
Keywords: Withania coagulans, Coronary artery disease, HMG-CoA reductase, Molegro virtual docker, Hypercholesterolemia, In silico studies