Abstract:
:Five series of novel thiophene-pyrimidine derivatives (9a-h, 10a-f, 11a-f, 12a-f, 13a-f) have been synthesized and tested for their anti-proliferative activity against several cancer cell lines in which EGF is highly expressed. Most of the target compounds showed excellent activity against one or more cancer cell lines. The most promising compound 13a, of which IC50 values on of cell lines A549 and A431 (4.34 ± 0.60 μM and 3.79 ± 0.57 μM) were similar to the lead compound Olmutinib, showed strong activity and selectivity to EGFRT790M and EGFRT790M/L858R. Inhibition data of human normal hepatoma cell line LO2 indicated that most target compounds were less toxic to normal cells and had selective inhibitory effects on cancer cells. In addition, the structure-activity relationship was analyzed and the mechanism of apoptosis induced by the 13a was studied. The results showed that compound 13a induced late apoptosis of A431 cancer cells in a dose-dependent manner.
journal_name
Eur J Med Chemjournal_title
European journal of medicinal chemistryauthors
Xiao Z,Zhou Z,Chu C,Zhang Q,Zhou L,Yang Z,Li X,Yu L,Zheng P,Xu S,Zhu Wdoi
10.1016/j.ejmech.2020.112511subject
Has Abstractpub_date
2020-10-01 00:00:00pages
112511eissn
0223-5234issn
1768-3254pii
S0223-5234(20)30483-9journal_volume
203pub_type
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