|Title||Advance of seriniquinone analogues as melanoma agents|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Hammons J.C, Trzoss L., Jimenez P.C, Hirata A.S, Costa-Lotufo L.V, La Clair J.J, Fenical W|
|Type of Article||Article|
|Keywords||dermcidin; drug discovery; epigenetics; kinase; marine natural products; medicinal chemistry; melanoma; Pharmacology & Pharmacy; seriniquinone; trametinib|
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.