Department of Chemistry and Center for Molecular Diversity in Drug Design, Discovery and Delivery, South Florida, Tampa, FL 33620, USA.
Bioorg Med Chem. 2011 Oct 1;19(19):5756-62. doi: 10.1016/j.bmc.2011.08.033. Epub 2011 Aug 22.
The marine invertebrate-derived meridianin A, the originally proposed structure for psammopemmin A, and several related 3-pyrimidylindole analogs were synthesized and subsequently investigated for central nervous system, antimalarial, and cytotoxic activity. A Suzuki coupling of an indoleborate ester to the pyrimidine electrophile was utilized to form the natural product and derivatives thereof. The 3-pyrimidineindoles were found to prevent radioligand binding to several CNS receptors and transporters, most notably, serotonin receptors (<0.2 μM K(i) for 5HT(2B)). Two compounds also inhibited the human malaria parasite Plasmodium falciparum (IC(50) <50 μM). Only the natural product was cytotoxic toward A549 cells (IC(50)=15 μM).
海洋无脊椎动物衍生的 meridianin A，最初被提议为 psammopemmin A 的结构，以及几种相关的 3-嘧啶吲哚类似物被合成，并随后对其进行了中枢神经系统、抗疟和细胞毒性活性的研究。利用吲哚硼酸酯与嘧啶亲电试剂的 Suzuki 偶联反应来形成天然产物及其衍生物。发现 3-嘧啶吲哚类化合物可防止放射性配体与几种中枢神经系统受体和转运体结合，尤其是 5-羟色胺受体（<0.2 μM K(i) 5HT(2B)）。两种化合物还抑制了人类疟原虫 Plasmodium falciparum（IC(50)<50 μM）。只有天然产物对 A549 细胞具有细胞毒性（IC(50)=15 μM）。
