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Molecular modeling and assessment of cytotoxic and apoptotic potentials of imatinib analogues featuring (thio)urea motifs in human leukemia and lymphoma cells

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dc.contributor.authorTÜRE, ASLI
dc.contributor.authorsBingol Ozakpinar, Ozlem; Ture, Asli; Kucukguzel, Ilkay
dc.date.accessioned2022-03-12T16:24:32Z
dc.date.available2022-03-12T16:24:32Z
dc.date.issued2020
dc.description.abstractImatinib is a well-known anticancer drug. In this study, cytotoxic properties of thirty-two imatinib analogues featuring (thio)urea motifs have been evaluated against chronic myeloid leukemia (K562), Burkitt lymphoma (Raji) and mouse embryonic fibroblast (NIH 3T3) cells. IC50 values of selected eleven compounds were calculated against K562 and NIH 3T3 cells. Apoptotic properties of the most active three compounds were evaluated on K652 cells subsequently. Favorably, compounds 19, 31 and 32 induced early apoptotic changes on K562 cells. Loss of membrane potential as well as caspase-3 and caspase-9 activation was determined in the present study. Levels of anti-apoptotic proteins, Bcl-XL and Bcl-2 decreased after the implementation of compounds 19, 31 and 32 at 10 mu M and 50 mu M concentrations. To reveal further molecular insight into the anticancer activity of the compounds, compounds 19, 31 and 32 were docked into ABL kinase protein as imatinib shows anticancer activity by inhibiting this enzyme. Modeling studies demonstrated significant molecular interactions between compounds 19, 31 and 32 and ABL protein. Compounds 19, 31 and 32 showed excellent superposition with imatinib in the binding site of ABL. These findings suggest that compounds 19, 31 and 32 have potential to show anticancer activity against chronic myeloid leukemia.
dc.identifier.doi10.35333/jrp.2020.239
dc.identifier.issn2630-6344
dc.identifier.urihttps://hdl.handle.net/11424/226373
dc.identifier.wosWOS:000592829900002
dc.language.isoeng
dc.publisherMARMARA UNIV
dc.relation.ispartofJOURNAL OF RESEARCH IN PHARMACY
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectImatinib analogues
dc.subjectABL kinase
dc.subjectchronic myeloid leukemia
dc.subjectlymphoma
dc.subjectmolecular modeling
dc.subjectdocking
dc.subjectABL TYROSINE KINASE
dc.subjectSORAFENIB
dc.subjectINHIBITION
dc.subjectDISCOVERY
dc.titleMolecular modeling and assessment of cytotoxic and apoptotic potentials of imatinib analogues featuring (thio)urea motifs in human leukemia and lymphoma cells
dc.typeconferenceObject
dspace.entity.typePublication
local.avesis.id942946db-3d93-4ab7-a617-3399c1b6a96f
local.conference.dateDEC 13-15, 2018
local.conference.locationIstanbul, TURKEY
local.conference.title6th International BAU Drug Design Congress
local.import.packageSS15
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atTRDIZIN
local.journal.numberofpages11
oaire.citation.endPage811
oaire.citation.issue6
oaire.citation.startPage801
oaire.citation.titleJOURNAL OF RESEARCH IN PHARMACY
oaire.citation.volume24
relation.isAuthorOfPublication515da16e-3e07-453b-bfbb-c60fbd768648
relation.isAuthorOfPublication.latestForDiscovery515da16e-3e07-453b-bfbb-c60fbd768648

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