Advance of Seriniquinone Analogues as Melanoma Agents

Author(s)

Hammons, Justin C. ^[1] ; Trzoss, Lynnie ^[1] ; Jimenez, Paula C. ^[2] ; Hirata, Amanda S. ^[3] ; Costa-Lotufo, Leticia V. ^[3] ; La Clair, James J. ^[4] ; Fenical, William ^[1]

Affiliation

^[1] Univ Calif San Diego, Scripps Inst Oceanog, Ctr Marine Biotechnol & Biomed, La Jolla, CA 92093 - USA

^[2] Univ Fed Sao Paulo, Inst Mar, BR-11070100 Santos, SP - Brazil

^[3] Univ Sao Paulo, Inst Ciencias Biomed, BR-05508900 Sao Paulo, SP - Brazil

^[4] Univ Calif San Diego, Dept Chem & Biochem, 9500 Gilman Dr, La Jolla, CA 92093 - USA

• Document type: Journal article
• Source: ACS Medicinal Chemistry Letters; v. 10, n. 2, p. 186-190, FEB 2019.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 16/10854-5 - Investigation of cytotoxic mechanisms of synthetic derivatives of seriniquinone in melanoma cell lines
• Grantee: Amanda Soares Hirata
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/07661-6 - Seriniquinone and its derivative LT406 as antimelanoma agents in experimental models
• Grantee: Amanda Soares Hirata
• Support Opportunities: Scholarships in Brazil - Master