BENGAMIDES and Derivatives

Bengamide A
Molecular Weight: 598.812 g/mol
Molecular Formula: C₃₂H₅₈N₂O₈

Bengamide B
Molecular Weight: 584.785 g/mol
Molecular Formula: C₃₁H₅₆N₂O₈

Source: Fijian sponges: unidentified Jaspidae, Jaspis cf. coriacea (PORIFERA)
Activity: tumor growth inhibitor
Status: Synthetic analog LAF389 withdrawn from Phase I clinical trials in 2002.

Two novel seven-membered ring heterocycles, bengamide A and bengamide B, were reported in 1986 isolated from an as yet undescribed Fijian sponge belonging to family Jaspidae. Since this time, a number of additional compounds from the bengamide class have been isolated, most notably from the Fijian sponge Jaspis cf. coriacea.

Bengamides A and B were initially reported to exhibit in vitro toxicity to larynx epithelial carcinoma cells, and to have antibiotic and anti-helminthic activity (against the nematode Nippostrongulus braziliensis) as well.

A synthetic bemgamide analog, LAF389, was developed and shown to inhibit certain tumor growth, apparently by means of methionine aminopeptidase inhibition. The pharmaceutical company Novartis (then Ciba-Geigy) brought LAF389 into Phase I clinical trials before deciding to withdraw this compound in 2002.

There is still ongoing research that is centered on the Bengamides and their derivatives. A report from late 2003 describes a proteomics-based investigation in which LAF389 was used to identify protein signaling pathways altered by bengamide addition.

NCBI PubChem compound summary page, Bengamide A - [ LINK ]

NCBI PubChem compound summary page, Bengamide B - [ LINK ]

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Newman DJ, and GM Cragg. 2004. Advanced Preclinical and Clinical trials of natural Products and Related Compounds from marine Sources. Current Medicinal Chemistry 11:1693-1713.

Thale Z, Kinder FR, Bair KW, Bontempo J, Czuchta AM, Versace RW, Phillips PE, Sanders ML, Wattanasin S, Crews P. 2001. Bengamides revisited: new structures and antitumor studies. J Org Chem. 9;66:1733-41.

Towbin H, Bair KW, DeCaprio JA, Eck MJ, Kim S, Kinder FR, Morollo A, Mueller DR, Schindler P, Song HK, van Oostrum J, Versace RW, Voshol H, Wood J, Zabludoff S, Phillips PE. 2003. Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors. J Biol Chem. 26;278:52964-71. A and P Sawangwong. 2004. Drugs and cosmetics from the sea (review paper). Mar. Drugs 2004:73-82.