CNS and antimalarial activity of synthetic meridianin and psammopemmin analogs.

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Lebar MD, Hahn KN, Mutka T, Maignan P, McClintock JB, Amsler CD, van Olphen A, Kyle DE, Baker BJ

CNS and antimalarial activity of synthetic meridianin and psammopemmin analogs.

Bioorg Med Chem. 2011 Oct 1;19(19):5756-62. doi: 10.1016/j.bmc.2011.08.033. Epub 2011 Aug 22.

PubMed ID

21907583 [ View in PubMed

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Abstract

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 muM K(i) for 5HT(2B)). Two compounds also inhibited the human malaria parasite Plasmodium falciparum (IC(50) <50 muM). Only the natural product was cytotoxic toward A549 cells (IC(50)=15 muM).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Chlorpromazine	5-hydroxytryptamine receptor 2C	Ki (nM)	27	N/A	N/A	Details
Chlorpromazine	5-hydroxytryptamine receptor 7	Ki (nM)	27	N/A	N/A	Details
Ergotamine	5-hydroxytryptamine receptor 1D	Ki (nM)	6	N/A	N/A	Details