Dual inhibitors of epidermal growth factor receptor and topoisomerase IIa derived from a quinoline scaffold

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dc.contributor.authorChauhan, Monika
dc.contributor.authorJoshi, Gaurav
dc.contributor.authorKler, Harveen
dc.contributor.authorKashyap, Archana
dc.contributor.authorAmrutkar, Suyog M.
dc.contributor.authorSharma, Praveen
dc.contributor.authorBhilare, Kiran D.
dc.contributor.authorBanerjee, Uttam C.
dc.contributor.authorSingh, Sandeep
dc.contributor.authorKumar, Raj
dc.date.accessioned2017-08-08T06:44:03Z
dc.date.accessioned2024-08-13T12:06:04Z
dc.date.available2017-08-08T06:44:03Z
dc.date.available2024-08-13T12:06:04Z
dc.date.issued2016
dc.description.abstractBased on the quinazoline bearing EGFR inhibitors, a series of thirty four compounds having a quinoline scaffold were synthesised and evaluated in vitro for EGFR kinase inhibitory activity. A structure-activity relationship study revealed that 2,4-bis(arylamino) substituted quinolines possessed better anti-EGFR kinase activity. Compounds 3f and 3m emerged as potent EGFR kinase inhibitors (200 and 210 nM, respectively) and showed excellent anticancer activity at the micromolar level against a panel of cancer cell lines comparable to erlotinib. Furthermore, representative compounds inhibited the human topoisomerase II? selectively and catalytically, did not intercalate with DNA, increased intracellular ROS concentration (except 3m) and altered the mitochondrial membrane potential of the cancer cells. Cell cycle analysis and annexin-V staining in a lung cancer cell line showed that the compounds delayed cell cycle progression by inducing cell cycle arrest and subsequent apoptosis at the G1 phase. The facts were further corroborated through molecular modeling studies. ? 2018 The Royal Society of Chemistry.en_US
dc.identifier.citationChauhan M, Sharma G, Kler H, Kashyap A, Amrutkar SM, Sharma P, et al. (2016) Dual inhibitors of epidermal growth factor receptor and topoisomerase IIa derived from a quinoline scaffold.RSC Advance;6 77717-34.en_US
dc.identifier.doi10.1039/c6ra15118c
dc.identifier.issnOnline- 2046-2069
dc.identifier.urihttp://10.2.3.109/handle/32116/298
dc.identifier.urlhttp://pubs.rsc.org/en/content/articlelanding/2016/ra/c6ra15118c#!divAbstract
dc.language.isoenen_US
dc.publisherRoyal Society of Chemistryen_US
dc.titleDual inhibitors of epidermal growth factor receptor and topoisomerase IIa derived from a quinoline scaffolden_US
dc.title.journalRSC Advances
dc.typeArticleen_US
dc.type.accesstypeClosed Accessen_US

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