Santacruzamate A, a potent and selective histone deacetylase inhibitor from the Panamanian marine cyanobacterium cf. Symploca sp

TitleSantacruzamate A, a potent and selective histone deacetylase inhibitor from the Panamanian marine cyanobacterium cf. Symploca sp
Publication TypeJournal Article
Year of Publication2013
AuthorsPavlik C.M, Wong C.YB, Ononye S., Lopez D.D, Engene N, McPhail K.L, Gerwick WH, Balunas M.J
JournalJournal of Natural Products
Volume76
Pagination2026-2033
Date Published2013/11
Type of ArticleArticle
ISBN Number0163-3864
Accession NumberWOS:000327677800003
Keywordsbiological evaluation; cancer; depsipeptide; discovery; drug; hdac inhibitors; information; lyngbya-majuscula; romidepsin; therapy
Abstract

A dark brown tuft-forming cyanobacterium, morphologically resembling the genus Symploca, was collected during an expedition to the Coiba National Park, a UNESCO World Heritage Site on the Pacific coast of Panama. Phylogenetic analysis of its 16S rRNA gene sequence indicated that it is 4.5% divergent from the type strain for Symploca and thus is likely a new genus. Fractionation of the crude extract led to the isolation of a new cytotoxin, designated santacruzamate A (1), which has several structural features in common with suberoylanilide hydroxamic acid [(2), SAHA, trade name Vorinostat], a clinically approved histone deacetylase (HDAC) inhibitor used to treat refractory cutaneous T-cell lymphoma. Recognition of the structural similarly of 1 and SAHA led to the characterization of santacruzamate A as a picomolar level selective inhibitor of HDAC2, a Class I HDAC, with relatively little inhibition of HDAC4 or HDAC6, both Class II HDACs. As a result, chemical syntheses of santacruzamate A as well as a structurally intriguing hybrid molecule, which blends aspects of both agents (1 and 2), were achieved and evaluated for their HDAC activity and specificity.

DOI10.1021/np400198r
Short TitleJ. Nat. Prod.
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