title: CNS and antimalarial activity of synthetic meridianin and psammopemmin analogs.
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 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).
authors: Department of Chemistry and Center for Molecular Diversity in Drug Design, Discovery and Delivery, South Florida, Tampa, FL 33620, USA.
authors: Matthew D
authors: MD
authors: Lebar
authors: Kristopher N
authors: KN
authors: Hahn
authors: Tina
authors: T
authors: Mutka
authors: Patrick
authors: P
authors: Maignan
authors: James B
authors: JB
authors: McClintock
authors: Charles D
authors: CD
authors: Amsler
authors: Alberto
authors: A
authors: van Olphen
authors: Dennis E
authors: DE
authors: Kyle
authors: Bill J
authors: BJ
authors: Baker
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002491:Central Nervous System Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011743:Pyrimidines / Q000737:chemistry; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism
chemical_list: D000962:Antimalarials; D002491:Central Nervous System Agents; D026121:Indole Alkaloids; D007211:Indoles; D011743:Pyrimidines; D011985:Receptors, Serotonin; C560347:meridianin A; C030986:pyrimidine