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.
Biomed Pharmacother. 2022 Sep;153:113494. doi: 10.1016/j.biopha.2022.113494. Epub 2022 Jul 30.
A range of novel 1,9-disubstituted β-carboline derivatives was designed, synthesized and evaluated as potential anticancer agents. The preliminary study suggested that compounds 6a, 6b, 6c, 6d, 6e, 6f, 6g, and 6h tested in this study exerted potent antiproliferative effects on ten selected human tumor cell lines, with compound 6e being the most effective antiproliferative agent against the BGC-823, A375 and HT-29 cell lines, with IC values of 23.9, 9.3, and 3.6 µM, respectively. In addition, the antitumor capability of compound 6e was also evaluated in vivo, which demonstrated that compound 6e distinctly inhibited colorectal tumor growth in syngeneic BALB/c mice. Further research into the fundamental mechanism revealed that compound 6e inhibited colorectal cancer growth through the ATG5 (autophagy-related-5)/ATG7 (autophagy-related-7)-dependent autophagy pathway. This research can contribute to further clinical application of β-carboline derivatives as new antitumor drugs.
设计、合成并评价了一系列新型 1,9-二取代β-咔啉衍生物，作为潜在的抗癌药物。初步研究表明，在所研究的化合物 6a、6b、6c、6d、6e、6f、6g 和 6h 中，有 10 种对所选的人肿瘤细胞系具有很强的增殖抑制作用，其中化合物 6e 对 BGC-823、A375 和 HT-29 细胞系的增殖抑制作用最为有效，IC 值分别为 23.9、9.3 和 3.6µM。此外，还在体内评估了化合物 6e 的抗肿瘤能力，结果表明，化合物 6e 明显抑制了同基因 BALB/c 小鼠的结直肠肿瘤生长。进一步研究其基本机制表明，化合物 6e 通过 ATG5（自噬相关-5）/ATG7（自噬相关-7）依赖性自噬途径抑制结直肠癌细胞生长。这项研究有助于进一步将β-咔啉衍生物临床应用于新型抗肿瘤药物。
