Volume: 40 Issue: 3
Detection of aroma compound’s binding mode conformations on anticancer target DNA topoisomerase II
Year: 2018, Page: 40-48, Doi: https://doi.org/10.62029/jmaps.v40i3.Kumar
Received: Nov. 27, 2018 Accepted: Dec. 18, 2018 Published: Dec. 31, 2018
Cancer is one of the most common, devastating class of disease affecting millions of people causing large number of death every year. It is therefore considered to be the second leading cause of death in developing countries next to cardiovascular diseases. Recent molecular studies have focussed on the most targeted gene for cancer i.e. DNA topoisomerase II (DNA TOP2), an enzyme that controls and alters the topological states of DNA during transcription. DNA TOP2 is also a target of known anticancer drugs like etoposide, doxorubicin, daunorubicin, amsacrine, amrubicin, and many others. These drugs have toxic properties and possess adverse side effects like cardiomyopathy, leading to congestive heart failure. Due to this reason, more active and safe drug are being searched worldwide. In this study, we performed virtual screening of natural compounds (small molecules) for the exploration of best fit compounds against DNA TOP2 through in silico molecular docking experiment and also evaluated the bioavailability and safety concern through electronic pharmacokinetics parameters (absorption, distribution, metabolism, excretion) compliance check-up and toxicity risk studies by using standard drugs. More than 1300 aroma compounds from AromaDb database were virtually docked on DNA TOP2 (PDB:1ZXM) for detection of the binding site, best fit binding mode conformation & their binding side residues by using FlexX docking software. Leads based on docking scores better than approved/investigational anticancer drugs targeting DNA TOP2 were prioritised. Total eight approved and five investigational anticancer drugs were used reported to bind with DNA TOP2. Results showed best fit 50 compounds with docking score (-44.05 to -26.85 kJ/mol), higher to standard drugs -16.88 to -38.27 kJ/mol and revealed four binding sites on DNA TOP2. This study suggest that virtually screened top 50 compounds may be used for preparation of aroma based herbal products with anticancer activity.
Keywords: Aroma compound's, AromaDb database, Cancer, DNA topoisomerase II, FlexX docking software
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© Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Lucknow (India)
Yogesh Kumar, Feroz Khan. 2018. Detection of aroma compound’s binding mode conformations on anticancer target DNA topoisomerase II. J Med Aromat Plant Sci 40: 40-48.
