Antineoplastic agents. 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (the Republic of Maldives).
The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10(-5) to 10(-7)% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 micrograms/mL) and 5 (1b, DU-145 prostate GI50 1.9 micrograms/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).
Pettit
G R
GR
Cancer Research Institute, Arizona State University, Tempe 85287-2404, USA.
Tan
R
R
Melody
N
N
Cichacz
Z A
ZA
Herald
D L
DL
Hoard
M S
MS
Pettit
R K
RK
Chapuis
J C
JC
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007195:Indian Ocean Islands; D007941:Leukemia P388; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011161:Porifera; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000737:chemistry* / Q000302:isolation & purification* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D013729:Terpenes; C116699:sesterstatin 4; C116700:sesterstatin 5