School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, Louisina, USA.
School of Sciences, College of Arts, Education & Sciences, University of Louisiana Monroe, Monroe, Louisina, USA.
Chem Biol Drug Des. 2022 Apr;99(4):620-633. doi: 10.1111/cbdd.14030. Epub 2022 Mar 1.
A series of pyrazolone compounds with different substitution patterns have been synthesized using microwave-assisted methods and evaluated their in vitro antiproliferative activity against human lung adenocarcinoma cell lines (A549 and NCI-H522). Among the tested compounds, the pyrazolone P7 exhibited high antiproliferative activity against both A549 and NCIH522 cancer cell lines while being 10 times less cytotoxic to non-cancerous cells. Moreover, our compounds P7 and P11 exhibited higher antiproliferative activity and selectivity against A549 and NCIH522 cells compared with the clinically approved drugs Afatinib and Gefitinib. The cell cycle analysis showed that the compound P7 and P11 arrests the cell cycle at G0/G1 phase, whereas the compounds P13 and P14 involved in G2/M phase arrest. The results from antiproliferative activity screening, cell cycle analysis, and kinase profiling indicate that the suitably substituted 1,3-diarylpyrazolones exhibit high antiproliferative activity against non-small cell lung cancer cells.
一系列具有不同取代模式的吡唑酮类化合物已通过微波辅助方法合成，并对其对人肺腺癌细胞系（A549 和 NCI-H522）的体外增殖抑制活性进行了评估。在所测试的化合物中，吡唑酮 P7 对 A549 和 NCIH522 癌细胞系表现出高增殖抑制活性，而对非癌细胞的细胞毒性低 10 倍。此外，与临床批准的药物阿法替尼和吉非替尼相比，我们的化合物 P7 和 P11 对 A549 和 NCIH522 细胞表现出更高的增殖抑制活性和选择性。细胞周期分析表明，化合物 P7 和 P11 将细胞周期阻滞在 G0/G1 期，而化合物 P13 和 P14 则参与 G2/M 期阻滞。增殖抑制活性筛选、细胞周期分析和激酶谱分析的结果表明，适当取代的 1,3-二芳基吡唑酮对非小细胞肺癌细胞表现出高增殖抑制活性。
