Cytotoxic constituents of the roots of Ekmanianthe longiflora.
Bioactivity-directed fractionation of the CHCl(3) extract of the roots of Ekmanianthe longiflora resulted in the isolation of three new natural products, (2R,3R,4R)-3,4-dihydro-3, 4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (1), (2S,3R, 4R)-3,4-dihydro-3, 4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone (2), and (2R, 3aR,9R,9aR)-9-hydroxy-2-(1-hydroxy-1-methylethyl)-2,3,3a,4,9 , 9a-hexahydro-naphtho[2,3-b]furan-4-one (3), together with the known compounds 2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-quinone (4), 2-acetylnaphtho[2,3-b]furan-4,9-quinone (5), dehydro-iso-alpha-lapachone (6), alpha-lapachone (7), catalponol, and epi-catalponol. The structures of 1-3 were determined using a combination of NMR spectroscopic techniques, and the absolute configurations of compounds 1 and 2 were obtained using Mosher ester methodology. Compounds 4-6 showed significant cytotoxicity in a panel of human cancer cells. alpha-Lapachone (7) exhibited only marginal activity, and catalponol and epi-catalponol were inactive in this regard. When tested at 72 mg/kg/injection in an in vivo mouse P-388 leukemia system, compound 4 was inactive (110% T/C).
Peraza-Sánchez
S R
SR
Program for Collaborative Research in the Pharmaceutical Sciences and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 60612, USA.
Chávez
D
D
Chai
H B
HB
Shin
Y G
YG
García
R
R
Mejía
M
M
Fairchild
C R
CR
Lane
K E
KE
Menendez
A T
AT
Farnsworth
N R
NR
Cordell
G A
GA
Pezzuto
J M
JM
Kinghorn
A D
AD
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D009284:Naphthols / Q000302:isolation & purification* / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D014407:Tumor Cells, Cultured
C409609:3,4-dihydro-3,4-dihydroxy-2-(3-methyl-2-butenyl)-1(2H)-naphthalenone; C409608:9-hydroxy-2-(1-hydroxy-1-methylethyl)-2,3,3a,4,9,9a-hexahydronaphtho(2,3-b)furan-4-one; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D009284:Naphthols