CNS and antimalarial activity of synthetic meridianin and psammopemmin analogs

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 Ki for 5HT2B). Two compounds also inhibited the human malaria parasite Plasmodium falciparum (IC50 <50 μM). Only the natural product was cytotoxic toward A549 cells (IC50 = 15 μM).

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 Ki for 5HT2B). Two compounds also inhibited the human malaria parasite Plasmodium falciparum (IC50 <50 μM). Only the natural product was cytotoxic toward A549 cells (IC50 = 15 μM).Figure optionsDownload as PowerPoint slide