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Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents

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dc.contributor.authorSanphanya K.
dc.contributor.authorWattanapitayakul S.K.
dc.contributor.authorPrangsaengtong O.
dc.contributor.authorJo M.
dc.contributor.authorKoizumi K.
dc.contributor.authorShibahara N.
dc.contributor.authorPriprem A.
dc.contributor.authorFokin V.V.
dc.contributor.authorVajragupta O.
dc.date.accessioned2021-04-05T03:34:20Z
dc.date.available2021-04-05T03:34:20Z
dc.date.issued2012
dc.date.issuedBE2555
dc.description.abstractNovel urea derivatives of alkynes have been designed, synthesized, and evaluated as potential cancer therapeutics leads. The most active 1-((3-chloromethyl)phenyl)-3-prop-2-ynylurea (1) exhibited cytotoxic effect against HELA and MCF-7 cell lines with IC 50 values of 1.55 μM and 1.48 μM, respectively. Further investigation on tube formation assay in human vein umbilical cells (HUVEC) demonstrated that 1 and methyl 4-(3-(3-ethynylureido)benzyloxy) benzoate (6) possess antiangiogenic activity, with minimum effective dose of 25 nM (for 1) and 6.25 μM (for 6). The ED 50 of 1 and 6 were found to be 0.26 μM and 17.52 μM, respectively. The results from in vitro tyrosine kinase assay indicated the EGFR inhibition of 1 over other kinases (VEGFR2, FGFR1 and PDGFRβ). The cytotoxicity of 1 against EGFR overexpressing cell line A431 (IC 50 36 nM) was comparable to that of erlotinib. The binding mode of 1 from docking simulation in the EGFR active site revealed that the urea motif formed hydrogen bonding with Lys745, Thr854 and Asp855 in hydrophobic pocket of EGFR. Compound 1 is considered as a potential lead for further optimization. © 2012 Elsevier Ltd. All rights reserved.
dc.format.mimetypeapplication/pdf
dc.identifier.citationBioorganic and Medicinal Chemistry Letters. Vol 22, No.8 (2012), p.3001-3005
dc.identifier.doi10.1016/j.bmcl.2012.02.029
dc.identifier.issn0960894X
dc.identifier.other2-s2.0-84859445159
dc.identifier.urihttps://hdl.handle.net/20.500.14740/7076
dc.rights.holderScopus
dc.subject.other1 [(3 chloromethyl)phenyl] 3 prop 2 ynylurea
dc.subject.other3 prop 2 ynylurea
dc.subject.other4 (3 (3 ethynylureido)benzyloxy) benzoate
dc.subject.otherAngiogenesis inhibitor
dc.subject.otherAntineoplastic agent
dc.subject.otherEpidermal growth factor receptor
dc.subject.otherErlotinib
dc.subject.otherProtein tyrosine kinase
dc.subject.otherUnclassified drug
dc.subject.otherVasculotropin receptor 2
dc.subject.otherArticle
dc.subject.otherCell strain MCF 7
dc.subject.otherCytotoxicity
dc.subject.otherDrug screening
dc.subject.otherDrug synthesis
dc.subject.otherHeLa cell
dc.subject.otherHuman
dc.subject.otherHuman cell
dc.subject.otherHydrogen bond
dc.subject.otherHydrophobicity
dc.subject.otherIn vitro study
dc.subject.otherAngiogenesis Inhibitors
dc.subject.otherBinding Sites
dc.subject.otherBreast Neoplasms
dc.subject.otherCell Line, Tumor
dc.subject.otherCell Proliferation
dc.subject.otherFemale
dc.subject.otherHeLa Cells
dc.subject.otherHumans
dc.subject.otherInhibitory Concentration 50
dc.subject.otherModels, Molecular
dc.subject.otherUrea
dc.titleSynthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents
dc.typeArticle
dspace.entity.typePublication
swu.datasource.scopushttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84859445159&doi=10.1016%2fj.bmcl.2012.02.029&partnerID=40&md5=34a7bad30c6025cd626fb50305c64ffc

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