Centro de Investigação em Química (CIQUP), Instituto de Ciências Moleculares (IMS), Departamento de Geociências, Ambiente e Ordenamento do Território, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal.
REQUIMTE/LAQV, Laboratory of Pharmacognosy, Department of Chemistry, Faculty of Pharmacy, University of Porto, R. Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Bioorg Chem. 2024 Mar;144:107083. doi: 10.1016/j.bioorg.2023.107083. Epub 2024 Jan 4.
Cancer is still one of the most challenging diseases to treat, making the pursuit for novel molecules with potential anticancer activity an important research topic. Herein, we have performed a comparative investigation into the anticancer activity of analogs of marine coelenterazine and coelenteramine. The former is a well-known bioluminescent substrate, while the latter is a metabolic product of the resulting bioluminescent reaction. While both types of analogs showed anticancer activity toward lung and gastric cancer cell lines, we have obtained data that highlight relevant differences between the activity of these two types of compounds. More specifically, we observed relevant differences in structure-activity relationships between these types of compounds. Also, coelenteramine analogs showed time-dependent activity, while coelenterazine-based compounds usually present time-independent activity. Coelenterazine analogs also appear to be relatively safer toward noncancer cells than coelenteramine analogs. There was also seen a correlation between the activity of the coelenterazine-based compounds and their light-emission properties. Thus, these results further indicate the potential of the marine coelenterazine chemi-/bioluminescent system as a source of new molecules with anticancer activity, while providing more insight into their modes of action.
癌症仍然是最难治疗的疾病之一，因此寻找具有潜在抗癌活性的新型分子是一个重要的研究课题。在这里，我们对海洋腔肠素和腔肠胺类似物的抗癌活性进行了比较研究。前者是一种众所周知的生物发光底物，而后者是生物发光反应的代谢产物。虽然这两种类似物都对肺癌和胃癌细胞系表现出抗癌活性，但我们获得的数据突出了这两种化合物活性之间的相关差异。更具体地说，我们观察到这两种类型的化合物之间的构效关系存在相关差异。此外，腔肠胺类似物表现出时间依赖性活性，而腔肠素类化合物通常表现出时间非依赖性活性。腔肠素类似物对非癌细胞的安全性似乎也相对高于腔肠胺类似物。基于腔肠素的化合物的活性与其发光特性之间也存在相关性。因此，这些结果进一步表明海洋腔肠素化学/生物发光系统作为具有抗癌活性的新型分子的潜在来源，同时为其作用模式提供了更多的见解。
