Mandelalides A-D, cytotoxic macrolides from a new Lissoclinum species of South African tunicate.
Mandelalides A-D are variously glycosylated, unusual polyketide macrolides isolated from a new species of Lissoclinum ascidian collected from South Africa, Algoa Bay near Port Elizabeth and the surrounding Nelson Mandela Metropole. Their planar structures were elucidated on submilligram samples by comprehensive analysis of 1D and 2D NMR data, supported by mass spectrometry. The assignment of relative configuration was accomplished by consideration of homonuclear and heteronuclear coupling constants in tandem with ROESY data. The absolute configuration was assigned for mandelalide A after chiral GC-MS analysis of the hydrolyzed monosaccharide (2-O-methyl-α-L-rhamnose) and consideration of ROESY correlations between the monosaccharide and aglycone in the intact natural product. The resultant absolute configuration of the mandelalide A macrolide was extrapolated to propose the absolute configurations of mandelalides B-D. Remarkably, mandelalide B contained the C-4' epimeric 2-O-methyl-6-dehydro-α-L-talose. Mandelalides A and B showed potent cytotoxicity to human NCI-H460 lung cancer cells (IC(50), 12 and 44 nM, respectively) and mouse Neuro-2A neuroblastoma cells (IC(50), 29 and 84 nM, respectively).
Department of Pharmaceutical Sciences, College of Pharmacy, 203 Pharmacy Building, Oregon State University, Corvallis, Oregon 97331, USA.
Justyna
J
Sikorska
Andrew M
AM
Hau
Clemens
C
Anklin
Shirley
S
Parker-Nance
Michael T
MT
Davies-Coleman
Jane E
JE
Ishmael
Kerry L
KL
McPhail
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D013019:South Africa; D013045:Species Specificity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014561:Urochordata / Q000737:chemistry*
D000970:Antineoplastic Agents; D018942:Macrolides