LAULIMALIDE (and Synthetic Analogs)

Source: The Pacific sponge Cacospongia mycofijiensis; also Hyatella sp., Fasciospongia sp., and Dactylospongia sp. (PORIFERA)
Activity: tubulin interactive agent
Status: Preclinical

Sometimes referred to as the fijianolides, the natural products laulimide and (the significantly less bioactive) isolaulimide were first extracted from the Pacific sponge Cacospongia mycofijiensis. Since their initial discovery, the compounds have been found in other unrelated sponge genera, and also in extracts from a sponge-grazing chromodorid nudibranch. A number of laboratory synthetic pathways for producing analogs of these natural compounds have been published.

The bioactivity displayed by these compounds is as microtubule stabilizing agents potentially arresting the development of target cells. The exact mode of action with regard to how and where the molecules bind tubulin has not been reported, but the activity profiles are clearly different from that of other microtubule-binding agents such as paclitaxel.

While naturally occurring laulimalide shows effectiveness against paclitaxel-resistant cells, the compound is intrinsically unstable. Recently, Mooberry and colleagues (2004) synthesized several laulimalide analogs designed to address this stability issue. Some of these retain the unique biological activities of the natural molecule, including effectiveness against paclitaxel- and epothilone-resistant cell lines.

Preclinical evaluation of these compounds is ongoing.

NCBI PubMed biomedical literature citations and abstracts - [ LINK ]

References

Mooberry SL, Randall-Hlubek DA, Leal RM, Hegde SG , Hubbard RD, Zhang L, and PA Wender. 2004. Microtubule-Stabilizing Agents Based on Designed Laulimalide Analogues. PNAS 101: 8803-8808.

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.