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Design and synthesis of phthalazine-based compounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition.
- Source :
-
Journal of Enzyme Inhibition & Medicinal Chemistry . Dec2019, Vol. 34 Issue 1, p1347-1367. 21p. - Publication Year :
- 2019
-
Abstract
- In the designed compounds, either a biarylamide or biarylurea moiety or an N-substituted piperazine motif was linked to position 1 of the phthalazine core. The anti-proliferative activity of the synthesised compounds revealed that eight compounds (6b, 6e, 7b, 13a, 13c, 16a, 16d and 17a) exhibited excellent broad spectrum cytotoxic activity in NCI 5-log dose assays against the full 60 cell panel with GI50 values ranging from 0.15 to 8.41 µM. Moreover, the enzymatic assessment of the synthesised compounds against VEGFR-2 tyrosine kinase showed the significant inhibitory activities of the biarylureas (12b, 12c and 13c) with IC50s of 4.4, 2.7 and 2.5 μM, respectively, and with 79.83, 72.58 and 71.6% inhibition of HUVEC at 10 μM, respectively. Additionally, compounds (7b, 13c and 16a) were found to induce cell cycle arrest at S phase boundary. Compound 7b triggered a concurrent increase in cleaved caspase-3 expression level, indicating the apoptotic-induced cell death. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14756366
- Volume :
- 34
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Enzyme Inhibition & Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 140468478
- Full Text :
- https://doi.org/10.1080/14756366.2019.1642883