Hammons Justin C, Trzoss Lynnie, Jimenez Paula C, Hirata Amanda S, Costa-Lotufo Leticia V, La Clair James J, Fenical William
Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California 92093-0204, United States.
Instituto do Mar, Universidade Federal de São Paulo, Santos, São Paulo 11070-100, Brazil.
ACS Med Chem Lett. 2019 Feb 6;10(2):186-190. doi: 10.1021/acsmedchemlett.8b00391. eCollection 2019 Feb 14.
Seriniquinone, a marine natural product, displayed potent cytotoxicity and selectivity against melanoma cancer cells. This selectivity, combined with a novel mode of action (MOA), prompted studies to translate a pharmacologically relevant lead. Herein, we report on structure-activity relationships (SARs), and provide a strategy to prepare analogues that retain activity and offer an improved water solubility and isomeric purity. From intermediates made on a gram-scale, derivatives were prepared and evaluated for their antiproliferation activity and melanoma selectivity. Overall these studies provide methods to install side chain motifs that demonstrate a common, and yet unique, biological profile.
海兔醌，一种海洋天然产物，对黑色素瘤癌细胞显示出强大的细胞毒性和选择性。这种选择性与一种新的作用模式（MOA）相结合，促使开展研究以转化具有药理学相关性的先导化合物。在此，我们报告结构-活性关系（SARs），并提供一种制备保留活性且具有改善的水溶性和异构体纯度的类似物的策略。从克级规模制备的中间体出发，制备了衍生物并评估其抗增殖活性和对黑色素瘤的选择性。总体而言，这些研究提供了安装侧链基序的方法，这些侧链基序展现出一种共同但又独特的生物学特征。
