Designing, molecular docking, and dynamics simulations studies of 1,2,3-triazole clamped Uracil-Coumarin hybrids against EGFR tyrosine kinase

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dc.contributor.authorSanduja, Mohiten_US
dc.contributor.authorGupta, Jyotien_US
dc.contributor.authorRawat, Ravien_US
dc.contributor.authorSingh, Uttamen_US
dc.contributor.authorVerma, Saurabh M.en_US
dc.date.accessioned2020-10-16T08:56:48Z
dc.date.available2020-10-16T08:56:48Z
dc.date.issued2020-03
dc.description.abstractSince the last decade, hybrid drug strategies have attracted many researchers for their improved anti-cancer potential incomparison to single drug components. Complying to this approach, 28 novel Uracil–Coumarin hybrids with differentsized linkers (2–5 carbon atoms) and substituents were designed to occupy the active site of protein epidermal growthfactor receptor (EGFR) tyrosine kinase (Protein Data Bank ID: 1M17). Molecular docking studies were performedfor all ligands (A1-D7) to identify the potential candidate using Schrödinger software. The relative binding affinity ofhybrids toward EGFR was compared with standard Erlotinib on the basis of gScore and Emodel score. Positively, allthe hybrids docked inside the cavity and showed significant interactions, compounds A6, A2, and A7 with short-chainlinker (two carbon atoms) and halogen substituents were found to have more interactions and better docking score thanstandard Erlotinib. The visualization results depicted that compound A6 showed the highest affinity and formed thebest binding pose to the target EGFR with gScore = −8.891 kcal/mol and Emodel score = −100.744 in comparison tostandard Erlotinib (gScore of −8.538 kcal/mol and Emodel score = −80.588). Moreover, a molecular dynamics studyalso reveals that ligand A6 forms a stable complex with root mean square deviation (RMSD) of 0.3 nm and the plateauphase started just after 10 ns (time). Hence, the present research provides computational insights of Uracil–Coumarinhybrids as potential ligands against EGFR tyrosine kinase and in future in vitro investigations of these hybrids mayprove their therapeutic potential against cancer.en_US
dc.identifier.affiliationsSchool of Pharmaceutical Sciences, MVN University, Palwal 121105, India.en_US
dc.identifier.affiliationsSchool of Pharmaceutical Sciences, MVN University, Palwal 121105, India.en_US
dc.identifier.affiliationsDepartment of Pharmaceutical Sciences &Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Indiaen_US
dc.identifier.affiliationsDepartment of Pharmaceutical Sciences &Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Indiaen_US
dc.identifier.affiliationsDepartment of Pharmaceutical Sciences &Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Indiaen_US
dc.identifier.citationSanduja Mohit, Gupta Jyoti, Rawat Ravi, Singh Uttam, Verma Saurabh M.. Designing, molecular docking, and dynamics simulations studies of 1,2,3-triazole clamped Uracil-Coumarin hybrids against EGFR tyrosine kinase. Journal of Applied Pharmaceutical Science. 2020 Mar; 2020 Mar: 001-011en_US
dc.identifier.issn2231-3354
dc.identifier.placeIndiaen_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/210699
dc.languageenen_US
dc.publisherOpen Science Publishers LLPen_US
dc.relation.issuenumber3en_US
dc.relation.volume10en_US
dc.source.urihttps://dx.doi.org//10.7324/JAPS.2020.103001en_US
dc.subjectUracilen_US
dc.subjectCoumarinen_US
dc.subjecthybrid moleculeen_US
dc.subjectEGFRen_US
dc.subjectErlotiniben_US
dc.subjectdockingen_US
dc.subjectdynamicsen_US
dc.titleDesigning, molecular docking, and dynamics simulations studies of 1,2,3-triazole clamped Uracil-Coumarin hybrids against EGFR tyrosine kinaseen_US
dc.typeJournal Articleen_US
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