Synthesis and antiproliferative evaluation of oxime, methyloxime, and amide‐containing quinazolinones

Abstract

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 IC50 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 IC50 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.

An Alkyne‐Bridged Covalent Organic Framework Featuring Interactive Pockets for Bromine Capture

“…This indicates that the bromine has been captured preferentially and the remaining solution contains mostly iodine. Since in iodine and bromine mixtures, an interhalogen compound (IBr) is also formed, it is crucial to analyze the possibility of the coexistence of Br 2 , I 2 , and IBr [35,36] in the solution and the capture capability of the material towards IBr. To evaluate this, solution Raman spectra were recorded for the individual solutions of iodine and bromine, as well as the equimolar iodine‐bromine mixture and of the iodine‐bromine mixture after exposure to the COF (Figure 2f).…”

Synthesis and antiproliferative evaluation of oxime, methyloxime, and amide‐containing quinazolinones

“…13 The colorimetric assay for cellular growth and survival was performed as described by Hansen et al, with slight modifications. [20] Pre-determined numbers of cells were seeded in a 96-well microplate, and designated compounds at various concentrations were added for the indicated time period. The MTT-containing solution was added after compound treatment, and conversion of MTT to formazan by metabolically viable cells was measured by absorbance at 490 nm in a 96-well microtiter plate reader.…”

Photogenerated chlorine radicals activate C(sp3)–H bonds of alkylbenzenes to access quinazolinones

“…Quinazolinones are important heterocycles in synthetic pharmaceuticals 1 and natural products, 2 and have been extensively studied because they are key structural motifs of drugs with antihypertensive, 3 anticancer, 4 anti-tubercular, 5 and anti-inflammatory activity. 2 a ,6 Furthermore, quinazolinones are also used as multifunctional directing groups (DG) in the preparation of heterocyclic scaffolds.…”