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Synthesis and antiproliferative evaluation of oxime, methyloxime, and amide‐containing quinazolinones
Author(s) -
Chang KenMing,
Chen LiChai,
Tzeng CherngChyi,
Lu YaoHua,
Chen ILi,
Juang ShinHun,
Wang TaiChi
Publication year - 2018
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.201700463
Subject(s) - chemistry , quinazolinone , jurkat cells , cell cycle , cell culture , oxime , cell cycle checkpoint , cytotoxicity , cell , microbiology and biotechnology , cancer research , stereochemistry , in vitro , biochemistry , t cell , immunology , immune system , genetics , biology
Certain oxime, methyloxime, and amide‐containing quinazolinone derivatives were synthesized and evaluated in vitro for their antiproliferative activities against a panel of human cancer cell lines including nasopharyngeal carcinoma (NPC‐TW01), lung carcinoma (NCI‐H226), and leukemia (Jurkat). Quinazolinone 2 was inactive against all three cell lines tested, while quinazolinone 4 was weakly active against both Jurkat and H226 cancer cells with IC 50 values of 6.55 and 12.27 μM, respectively, indicating that the oxime derivative 4 is more favorable than its ketone precursor 2 . Our results have also indicated that quinazolinone 8g and its biphenyl counterpart 8f exhibited more potent antiproliferative activities than the positive control methotrexate against all three cancer cell lines tested. Among these quinazolinone derivatives, 8g was the most active against NPC‐TW01 with an IC 50 value of 4.78 μM. Further study on NPC‐TW01 cell cycle distribution indicated that the compound 8g induced cell arrest at the G1/G0 phase in a time‐ and concentration‐dependent manner. Moreover, a characteristic hypo‐diploid DNA content peak (sub‐G1) was found to increase from 1 to 4% in NPC‐TW01 cells treated with 8g for 72 hr. These results indicate that 8g can induce cells arrest in the G1/G0 phase and cause cell death. Further structural optimization of 8g and detailed study of its antiproliferative mechanism are going on.