title: Evaluation of pyridoacridine alkaloids in a zebrafish phenotypic assay.
abstract: Three new minor components, the pyridoacridine alkaloids 1-hydroxy-deoxyamphimedine (1), 3-hydroxy-deoxyamphimedine (2), debromopetrosamine (3), and three known compounds, amphimedine (4), neoamphimedine (5) and deoxyamphimedine (6), have been isolated from the sponge Xestospongia cf. carbonaria, collected in Palau. Structures were assigned on the basis of extensive 1D and 2D NMR studies as well as analysis by HRESIMS. Compounds 1-6 were evaluated in a zebrafish phenotype-based assay. Amphimedine (4) was the only compound that caused a phenotype in zebrafish embryos at 30 muM. No phenotype other than death was observed for compounds 1-3, 5, 6.
authors.affiliation: Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA. xiaomei.wei@pharm.utah.edu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wei
authors.forename: Tim S
authors.initials: TS
authors.lastname: Bugni
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Harper
authors.forename: Imelda T
authors.initials: IT
authors.lastname: Sandoval
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Manos
authors.forename: Jennifer
authors.initials: J
authors.lastname: Swift
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Van Wagoner
authors.forename: David A
authors.initials: DA
authors.lastname: Jones
authors.forename: Chris M
authors.initials: CM
authors.lastname: Ireland
mesh_terms: D000166:Acridines / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D000818:Animals; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity; D055808:Drug Discovery / Q000379:methods*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000473:pathology; D047108:Embryonic Development / Q000187:drug effects; D017403:In Situ Hybridization; D009672:Notochord / Q000187:drug effects / Q000473:pathology; D010140:Pacific Ocean; D019029:Palau; D010618:Phenanthrolines / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D019170:Somites / Q000187:drug effects / Q000473:pathology; D013723:Teratogens / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity*; D014020:Tissue Extracts / Q000737:chemistry; D018675:Toxicity Tests; D047131:Xestospongia / Q000737:chemistry; D015027:Zebrafish
chemical_list: D000166:Acridines; D003603:Cytotoxins; D010618:Phenanthrolines; D013723:Teratogens; D014020:Tissue Extracts; C475901:amphimedine