Evaluation of pyridoacridine alkaloids in a zebrafish phenotypic assay.
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.
Wei
Xiaomei
X
Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112, USA. xiaomei.wei@pharm.utah.edu
Bugni
Tim S
TS
Harper
Mary Kay
MK
Sandoval
Imelda T
IT
Manos
Elizabeth J
EJ
Swift
Jennifer
J
Van Wagoner
Ryan M
RM
Jones
David A
DA
Ireland
Chris M
CM
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
D000166:Acridines; D003603:Cytotoxins; D010618:Phenanthrolines; D013723:Teratogens; D014020:Tissue Extracts; C475901:amphimedine