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https://ir.swu.ac.th/jspui/handle/123456789/14351| Title: | Synthesis and evaluation of 1-(substituted)-3-prop-2-ynylureas as antiangiogenic agents |
| Authors: | Sanphanya K. Wattanapitayakul S.K. Prangsaengtong O. Jo M. Koizumi K. Shibahara N. Priprem A. Fokin V.V. Vajragupta O. |
| Keywords: | 1 [(3 chloromethyl)phenyl] 3 prop 2 ynylurea 3 prop 2 ynylurea 4 (3 (3 ethynylureido)benzyloxy) benzoate angiogenesis inhibitor antineoplastic agent epidermal growth factor receptor erlotinib protein tyrosine kinase unclassified drug vasculotropin receptor 2 article cell strain MCF 7 cytotoxicity drug screening drug synthesis HeLa cell human human cell hydrogen bond hydrophobicity in vitro study Angiogenesis Inhibitors Binding Sites Breast Neoplasms Cell Line, Tumor Cell Proliferation Female HeLa Cells Humans Inhibitory Concentration 50 Models, Molecular Urea |
| Issue Date: | 2012 |
| 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. |
| URI: | https://ir.swu.ac.th/jspui/handle/123456789/14351 https://www.scopus.com/inward/record.uri?eid=2-s2.0-84859445159&doi=10.1016%2fj.bmcl.2012.02.029&partnerID=40&md5=34a7bad30c6025cd626fb50305c64ffc |
| ISSN: | 0960894X |
| Appears in Collections: | Scopus 1983-2021 |
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