Advance of Seriniquinone Analogues as Melanoma Agents

  • ACS Med Chem Lett. 2019 Feb 6;10(2):186-190. doi: 10.1021/acsmedchemlett.8b00391.
Justin C Hammons  1 ,  Lynnie Trzoss  1 ,  Paula C Jimenez  2 ,  Amanda S Hirata  3 ,  Leticia V Costa-Lotufo  3 ,  James J La Clair  4 ,  William Fenical  1
Affiliations
  • 1. Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, California 92093-0204, United States.
  • 2. Instituto do Mar, Universidade Federal de São Paulo, Santos, São Paulo 11070-100, Brazil.
  • 3. Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, São Paulo 05508-900, Brazil.
  • 4. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, United States.
PMID: 30783501 DOI: 10.1021/acsmedchemlett.8b00391
Abstract

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.