Biological activities of novel pyrazolyl hydroxamic acid derivatives against human lung cancer cell line A549

• New pyrazolyl hydroxamic acid derivatives (4a–4l) were synthesized.
• Compounds 4a–4l inhibited the growth of A549 cancer cells.
• Compounds 4b, 4f and 4h induced cell cycle arrest at G1 phase.
• Compounds 4b, 4f and 4h are effective autophagy inducers.

We synthesized a series of novel pyrazolyl hydroxamic acid derivatives (4a–4l) and investigated their biological activities against human lung cancer cell line A549 in vitro to determine their mechanism of action. The results showed that the majority of derivatives had inhibitory effects on the growth of A549 cancer cells in dose and time-dependent manners, in which the compounds 4b, 4f, 4h and 4j (10 μM) exerted more effective anti-proliferation activity. However, it should be noted that 4j may result in necrosis at 10 μM. Furthermore, the three compounds 4b, 4f and 4h induced cell cycle arrest at G1 phase and triggered autophagy, but could not obviously induce apoptosis and necrosis under the stimulatory condition. Therefore, the pyrazolyl hydroxamic acid derivatives 4b, 4f and 4h can be used to investigate the regulatory mechanism of autophagy and offer new approaches to the prevention of lung cancer.

Figure optionsDownload as PowerPoint slide