Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, Granada 18100, Spain.
Department of Anatomy and Embriology, Faculty of Medicine, University of Granada, Granada 18071, Spain.
Mar Drugs. 2020 May 2;18(5):240. doi: 10.3390/md18050240.
The limited success and side effects of the current chemotherapeutic strategies against colorectal cancer (CRC), the third most common cancer worldwide, demand an assay with new drugs. The prominent antitumor activities displayed by the bengamides (Ben), a family of natural products isolated from marine sponges of the family, were explored and investigated as a new option to improve CRC treatment. To this end, two potent bengamide analogues, Ben I () and Ben V (), were selected for this study, for which they were synthesized according to a new synthetic strategy recently developed in our laboratories. Their antitumor effects were analyzed in human and mouse colon cell lines, using cell cycle analysis and antiproliferative assays. In addition, the toxicity of the selected analogues was tested in human blood cells. These biological studies revealed that Ben I and V produced a significant decrease in CRC cell proliferation and induced a significant cell cycle alteration with a greater antiproliferative effect on tumor cell lines than normal cells. Interestingly, no toxicity effects were detected in blood cells for both compounds. All these biological results render the bengamide analogues Ben I and Ben V as promising antitumoral agents for the treatment of CRC.
针对结直肠癌（CRC）的当前化疗策略的有限成功和副作用，CRC 是全球第三大常见癌症，需要进行新药物的试验。从海洋海绵家族中分离出的天然产物苯并酰胺（Ben）家族所表现出的显著抗肿瘤活性，被探索并研究作为改善 CRC 治疗的新选择。为此，选择了两种有效的苯并酰胺类似物 Ben I（）和 Ben V（）进行这项研究，根据我们实验室最近开发的新合成策略对它们进行了合成。在人源和鼠源结肠细胞系中分析了它们的抗肿瘤作用，使用细胞周期分析和抗增殖测定。此外，还在人血红细胞中测试了选定类似物的毒性。这些生物学研究表明，Ben I 和 V 显著降低了 CRC 细胞的增殖，并诱导了显著的细胞周期改变，对肿瘤细胞系的增殖抑制作用大于正常细胞。有趣的是，两种化合物在血红细胞中均未检测到毒性作用。所有这些生物学结果表明，苯并酰胺类似物 Ben I 和 Ben V 是治疗 CRC 的有前途的抗肿瘤药物。
