Ao Jingsheng, Zeng Feng, Wang Longhao, Qiu Liqin, Cao Rihui, Li Xiangpan
School of Chemistry, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou, 510275, PR China; Department of Oncology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, 430072, PR China.
Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, 430072, PR China.
Eur J Med Chem. 2023 Jan 15;246:114955. doi: 10.1016/j.ejmech.2022.114955. Epub 2022 Nov 26.
A series of novel β-carboline derivatives was designed, synthesized and evaluated as potential anticancer agents. Among them, compound 6g showed the most potent antiproliferative activity against the 786-0, HT-29 and 22RV1 cell lines with IC values of 2.71, 2.02, and 3.86 μM, respectively. The antitumor efficiency of compound 6gin vivo was also evaluated, and the results revealed that compound 6g significantly suppressed tumor development and reduced tumor weight in a mouse colorectal cancer homograft model. Further investigation on mechanisms of action demonstrated that compound 6g inhibited HCT116 cell growth by stimulating the ATG5/ATG7-dependent autophagic pathway. These molecules might be served as candidates for further development of colorectal cancer therapy agent.
设计、合成并评估了一系列新型β-咔啉衍生物作为潜在的抗癌药物。其中，化合物6g对786-0、HT-29和22RV1细胞系表现出最有效的抗增殖活性，IC值分别为2.71、2.02和3.86μM。还评估了化合物6g在体内的抗肿瘤效率，结果表明化合物6g在小鼠结直肠癌同种移植模型中显著抑制肿瘤发展并减轻肿瘤重量。对作用机制的进一步研究表明，化合物6g通过刺激ATG5/ATG7依赖性自噬途径抑制HCT116细胞生长。这些分子可能作为结直肠癌治疗药物进一步开发的候选物。
