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.

中文翻译：

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Santacruzamate A，一种来自巴拿马海洋蓝藻的强效选择性组蛋白脱乙酰酶抑制剂，参见。Symploca sp.

在前往巴拿马太平洋沿岸联合国教科文组织世界遗产科伊巴国家公园的探险中收集了一种在形态上类似于Symploca属的深棕色形成簇状蓝藻。对其 16S rRNA 基因序列的系统发育分析表明，它与Symploca的类型菌株有 4.5% 的差异，因此很可能是一个新属。粗提物的分馏导致分离出一种新的细胞毒素，命名为 santacruzamate A ( 1 )，它与辛二酰苯胺异羟肟酸具有几个共同的结构特征 [( 2)，SAHA，商品名 Vorinostat]，一种临床批准的组蛋白去乙酰化酶 (HDAC) 抑制剂，用于治疗难治性皮肤 T 细胞淋巴瘤。对1和 SAHA结构相似性的识别导致将 santacruzamate A 表征为 HDAC2（I 类 HDAC）的皮摩尔级选择性抑制剂，对 HDAC4 或 HDAC6（II 类 HDAC）的抑制相对较小。结果，实现了 santacruzamate A 以及结构上有趣的杂化分子的化学合成，该分子融合了两种药物（1和2）的各个方面，并评估了它们的 HDAC 活性和特异性。