Synthesis and Biological Evaluation of (<i>S</i>)-2-(Substituted arylmethyl)-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-<i>a</i>]indole-3-carboxamide Analogs and Their Synergistic Effect against PTEN-Deficient MDA-MB-468 Cells
A series of twenty-six compounds of furfuryl or benzyl tetrahydropyrazino[1,2-<i>a</i>]indole analogs were synthesized and evaluated for cytotoxic activity against the estrogen receptor (ER)-positive breast cancer cell line (MCF-7) and the epidermal growth factor receptor (EGFR) over-exp...
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| Main Authors: | , , , |
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| Format: | Book |
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MDPI AG,
2021-09-01T00:00:00Z.
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| Summary: | A series of twenty-six compounds of furfuryl or benzyl tetrahydropyrazino[1,2-<i>a</i>]indole analogs were synthesized and evaluated for cytotoxic activity against the estrogen receptor (ER)-positive breast cancer cell line (MCF-7) and the epidermal growth factor receptor (EGFR) over-expressed triple-negative breast cancer cell line (MDA-MB-468). Among them, compounds <b>2b</b>, <b>2f</b> and <b>2i</b> showed more potent activity and selectivity against MDA-MB-468 cells than gefitinib, as an EGFR- tyrosine kinase inhibitor. In addition, it was confirmed by means of isobologram analysis of combinational treatment with gefitinib that they have a synergistic effect, especially compounds <b>2b</b> and <b>2f</b>, which inhibit Akt T308 phosphorylation. Moreover, it was confirmed that 2-benzyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-<i>a</i>]indole-3-carboxamide analogs (<b>2b</b>, <b>2f</b>, and Ref 2) tend to selectively inhibit PI3Kβ, which is involved in the phosphorylation of Akt. |
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| Item Description: | 10.3390/ph14100974 1424-8247 |