Design and synthesis of phthalazine-based compounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition
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 ex...
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| Format: | Book |
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Taylor & Francis Group,
2019-01-01T00:00:00Z.
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| 001 | doaj_9a947ec1fa2c480bb7cdaa3d6abd3640 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Salwa Elmeligie |e author |
| 700 | 1 | 0 | |a Asmaa M. Aboul-Magd |e author |
| 700 | 1 | 0 | |a Deena S. Lasheen |e author |
| 700 | 1 | 0 | |a Tamer M. Ibrahim |e author |
| 700 | 1 | 0 | |a Tamer M. Abdelghany |e author |
| 700 | 1 | 0 | |a Sohair M. Khojah |e author |
| 700 | 1 | 0 | |a Khaled A. M. Abouzid |e author |
| 245 | 0 | 0 | |a Design and synthesis of phthalazine-based compounds as potent anticancer agents with potential antiangiogenic activity via VEGFR-2 inhibition |
| 260 | |b Taylor & Francis Group, |c 2019-01-01T00:00:00Z. | ||
| 500 | |a 1475-6366 | ||
| 500 | |a 1475-6374 | ||
| 500 | |a 10.1080/14756366.2019.1642883 | ||
| 520 | |a 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. | ||
| 546 | |a EN | ||
| 690 | |a substituted phthalazines | ||
| 690 | |a vegfr-2 kinase inhibitors | ||
| 690 | |a anti-proliferative | ||
| 690 | |a apoptosis | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 34, Iss 1, Pp 1347-1367 (2019) | |
| 787 | 0 | |n http://dx.doi.org/10.1080/14756366.2019.1642883 | |
| 787 | 0 | |n https://doaj.org/toc/1475-6366 | |
| 787 | 0 | |n https://doaj.org/toc/1475-6374 | |
| 856 | 4 | 1 | |u https://doaj.org/article/9a947ec1fa2c480bb7cdaa3d6abd3640 |z Connect to this object online. |