Antiproliferative Evaluation of Novel 4-Imidazolidinone Derivatives as Anticancer Agent Which Triggers ROS-Dependent Apoptosis in Colorectal Cancer Cell

Abstract

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 9r exhibited the best anticancer activity in CRC cell lines HCT116 and SW620. We further investigated the anticancer molecular mechanism of compound 9r. We found that compound 9r 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 9r-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 9r-induced apoptosis in CRC cells. The present results suggest that compound 9r has a potential therapeutic role in CRC. Hence, it deserves further exploration as a lead compound for CRC treatment.

Imidazolidinones Derivatives As Pioneering Anticancer Agents: Unraveling Insights Through synthesis And Structure‐Activity Exploration

“…N‐acetylcysteine (NAC), an antioxidant reagent, effectively mitigated 9r‐induced ROS production, JNK pathway activation, and apoptosis. These findings highlight the therapeutic potential of compound 9r in CRC treatment, warranting further investigation as a promising lead compound [22] …”

“…These findings highlight the therapeutic potential of compound 9r in CRC treatment, warranting further investigation as a promising lead compound. [22] El-Sayed et al ( 2018) designed and analyzed numerous compounds for treating cancer by mixing 4H-imidazole-4-one and imidazolidine-2,4-dione. The study used various cancer cell lines, such as PC-3 prostate cancer, HCT-116 colorectal carcinoma, MCF-7 breast cancer, and HeLa epithelioid carcinoma, to evaluate the IC 50 values of the created molecules.…”