Advance of seriniquinone analogues as melanoma agents

Citation:
Hammons, JC, Trzoss L, Jimenez PC, Hirata AS, Costa-Lotufo LV, La Clair JJ, Fenical W.  2019.  Advance of seriniquinone analogues as melanoma agents. Acs Medicinal Chemistry Letters. 10:186-190.

Date Published:

2019/02

Keywords:

dermcidin, drug discovery, epigenetics, kinase, marine natural products, medicinal chemistry, melanoma, Pharmacology & Pharmacy, seriniquinone, trametinib

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.

Notes:

n/a

Website

DOI:

10.1021/acsmedchemlett.8b00391