dc.contributor.author |
Sanphanya K. |
|
dc.contributor.author |
Wattanapitayakul S.K. |
|
dc.contributor.author |
Prangsaengtong O. |
|
dc.contributor.author |
Jo M. |
|
dc.contributor.author |
Koizumi K. |
|
dc.contributor.author |
Shibahara N. |
|
dc.contributor.author |
Priprem A. |
|
dc.contributor.author |
Fokin V.V. |
|
dc.contributor.author |
Vajragupta O. |
|
dc.date.accessioned |
2021-04-05T03:34:20Z |
|
dc.date.available |
2021-04-05T03:34:20Z |
|
dc.date.issued |
2012 |
|
dc.identifier.issn |
0960894X |
|
dc.identifier.other |
2-s2.0-84859445159 |
|
dc.identifier.uri |
https://ir.swu.ac.th/jspui/handle/123456789/14351 |
|
dc.identifier.uri |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84859445159&doi=10.1016%2fj.bmcl.2012.02.029&partnerID=40&md5=34a7bad30c6025cd626fb50305c64ffc |
|
dc.description.abstract |
Novel 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.subject |
1 [(3 chloromethyl)phenyl] 3 prop 2 ynylurea |
|
dc.subject |
3 prop 2 ynylurea |
|
dc.subject |
4 (3 (3 ethynylureido)benzyloxy) benzoate |
|
dc.subject |
angiogenesis inhibitor |
|
dc.subject |
antineoplastic agent |
|
dc.subject |
epidermal growth factor receptor |
|
dc.subject |
erlotinib |
|
dc.subject |
protein tyrosine kinase |
|
dc.subject |
unclassified drug |
|
dc.subject |
vasculotropin receptor 2 |
|
dc.subject |
article |
|
dc.subject |
cell strain MCF 7 |
|
dc.subject |
cytotoxicity |
|
dc.subject |
drug screening |
|
dc.subject |
drug synthesis |
|
dc.subject |
HeLa cell |
|
dc.subject |
human |
|
dc.subject |
human cell |
|
dc.subject |
hydrogen bond |
|
dc.subject |
hydrophobicity |
|
dc.subject |
in vitro study |
|
dc.subject |
Angiogenesis Inhibitors |
|
dc.subject |
Binding Sites |
|
dc.subject |
Breast Neoplasms |
|
dc.subject |
Cell Line, Tumor |
|
dc.subject |
Cell Proliferation |
|
dc.subject |
Female |
|
dc.subject |
HeLa Cells |
|
dc.subject |
Humans |
|
dc.subject |
Inhibitory Concentration 50 |
|
dc.subject |
Models, Molecular |
|
dc.subject |
Urea |
|
dc.title |
Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents |
|
dc.type |
Article |
|
dc.rights.holder |
Scopus |
|
dc.identifier.bibliograpycitation |
Bioorganic and Medicinal Chemistry Letters. Vol 22, No.8 (2012), p.3001-3005 |
|
dc.identifier.doi |
10.1016/j.bmcl.2012.02.029 |
|