College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, IATTI, Chongqing University of Arts and Sciences, Chongqing 402160, China.
College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
Molecules. 2022 Dec 13;27(24):8844. doi: 10.3390/molecules27248844.
Colorectal cancer (CRC) is one of the most common causes of cancer-related death worldwide, and more therapies are needed to treat CRC. To discover novel CRC chemotherapeutic molecules, we used a series of previously synthesized novel imidazolidin-4-one derivatives to study their anticancer role in several cancer cell lines. Among these compounds, compound exhibited the best anticancer activity in CRC cell lines HCT116 and SW620. We further investigated the anticancer molecular mechanism of compound . We found that compound induced mitochondrial pathway apoptosis in HCT116 and SW620 cells by inducing reactive oxygen species (ROS) production. Moreover, the elevated ROS generation activated the c-Jun N-terminal kinase (JNK) pathway, which further accelerated apoptosis. N-acetylcysteine (NAC), an antioxidant reagent, suppressed compound -induced ROS production, JNK pathway activation, and apoptosis. Collectively, this research synthesized a series of imidazolidin-4-one derivatives, evaluated their anticancer activity, and explored the molecular mechanism of compound -induced apoptosis in CRC cells. The present results suggest that compound has a potential therapeutic role in CRC. Hence, it deserves further exploration as a lead compound for CRC treatment.
结直肠癌(CRC)是全球癌症相关死亡的最常见原因之一,需要更多的治疗方法来治疗 CRC。为了发现新的 CRC 化疗分子,我们使用了一系列先前合成的新型咪唑烷-4-酮衍生物来研究它们在几种癌细胞系中的抗癌作用。在这些化合物中,化合物在 CRC 细胞系 HCT116 和 SW620 中表现出最好的抗癌活性。我们进一步研究了化合物的抗癌分子机制。我们发现化合物通过诱导活性氧(ROS)的产生诱导线粒体途径凋亡在 HCT116 和 SW620 细胞中。此外,升高的 ROS 生成激活了 c-Jun N-末端激酶(JNK)途径,从而进一步加速了细胞凋亡。抗氧化剂试剂 N-乙酰半胱氨酸(NAC)抑制了化合物诱导的 ROS 产生、JNK 途径激活和细胞凋亡。总之,本研究合成了一系列咪唑烷-4-酮衍生物,评估了它们的抗癌活性,并探讨了化合物诱导 CRC 细胞凋亡的分子机制。这些结果表明,化合物在 CRC 中具有潜在的治疗作用。因此,它值得进一步探索作为 CRC 治疗的先导化合物。