New structures and bioactivity properties of jasplakinolide (jaspamide) analogues from marine sponges.
The goal of this study was to isolate and study additional jasplakinolide analogues from two taxonomically distinct marine sponges including two Auletta spp. and one Jaspis splendens. This led to the isolation of jasplakinolide (1) and eleven jasplakinolide analogues (3-13) including seven new analogues (6-10, 12, and 13). Structure elucidation of the new compounds was based on a combination of 1D and 2D NMR analysis, optical rotation, circular dichroism, and preparation of Mosher's esters. Five of the new compounds are oxidized tryptophan derivatives of 1, including a unique quinazoline derivative (9). Compounds 1, 3, 5-8, and 11 were evaluated in the NCI 60 cell line screen, and all compounds were tested in a microfilament disruption assay. Jasplakinolide B (11) exhibited potent cytotoxicity (GI(50) < 1 nM vs human colorectal adenocarcinoma (HCT-116) cells) but did not exhibit microfilament-disrupting activity at 80 nM.
Robinson
Sarah J
SJ
Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz,California 95064, USA.
Morinaka
Brandon I
BI
Amagata
Taro
T
Tenney
Karen
K
Bray
Walter M
WM
Gassner
Nadine C
NC
Lokey
R Scott
RS
Crews
Phillip
P
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D047630:Depsipeptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011161:Porifera / Q000737:chemistry*; D011799:Quinazolines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013237:Stereoisomerism; D014364:Tryptophan / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D000970:Antineoplastic Agents; D047630:Depsipeptides; D011799:Quinazolines; C057531:jasplakinolide; D014364:Tryptophan