Bengamides revisited: new structures and antitumor studies.
The structural chemistry and biological activity of the bengamide class of compounds have been further characterized. Extracts prepared from recollected Jaspis cf. coriacea from five sites in Fiji were pooled. Six new bengamides, M (7b), N (8a), O (8b), P (9a), Q (9b), and R (10), were identified, accompanied by the known bengamides A (1a), B (1b), E (3a), F (3b), Y (5), Z (6), L (7a), G (11a), H (11b), and I (12). The structures of the new compounds were determined from spectroscopic data, and some were additionally confirmed by semisynthesis. Cytotoxicity screening data were obtained from the NCI-DTP 60 cell screen for bengamides A, B, and P. Bengamides A and B were more potent than bengamide P, with average IC(50) values of 0.046, 0.011, and 2.70 FM, respectively. The in vitro antitumor activity against MDA-MB-435 human mammary carcinoma was also determined for natural bengamides A, B, E, F, P, M, O, and Z and for synthetic samples of B and O. The best activity was observed for the natural bengamides A (IC(50) = 1 nM) and O (IC(50) = 0.3 nM).
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
Z
Z
Thale
F R
FR
Kinder
K W
KW
Bair
J
J
Bontempo
A M
AM
Czuchta
R W
RW
Versace
P E
PE
Phillips
M L
ML
Sanders
S
S
Wattanasin
P
P
Crews
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001381:Azepines