Lamellarins cytotoxicity activity

While for the pyrrole derived lamellarins and related compounds no activity has been described, several pentacyclic lamellarins show important cytotoxic activities. Lamellarin D at a concentration of 19 pg/ml caused a 78% inhibition of cell division in the fertilized sea urchin egg assay while lamellarin C caused 15% inhibition but lamellarins A and B were inactive <85JA5492>. Lamellarins I, K and L present significant cytotoxicity against P338 and A549 cultured cell lines and lamellarins K and L also exhibit immunomodulatory activity <93AJC489>. 

Lamellarins and related derivatives have many biological activities, such as antibiotic, cytotoxic, antitumor, reversal of multidrug resistance (MDR) and immunomodulatory activities, for which many details are given by Fan et al. (2008). Lamellarin D is also a powerful inhibitor of topoisomerase I, and an inducer of apoptosis (Facompre et al., 2003 Van-huyse et al., 2005). The synthesis and evaluation of a dozen structural analogs of lamellarin D has shown that the hydroxy groups at positions C-8 and C-20 are essential for its cytotoxic activity (Ishibashi et al., 2002 Bailly, 2004 Chittchang et al., 2010). 

The lamellarins generally do not exhibit much antimicrobial activity, but do show significant differential cytotoxicity. Lamellarin D was reported to cause 78% inhibition of development of fertilised sea urchin eggs at 19 pg/mL, while lamellarin C reportedly caused only 15% inhibition, and lamellarins A and B were inactive at the same concentration [50]. No activity data has been reported for lamellarins E - H, while from results of preliminary testing, lamellarins I, K and L were reported to show comparable and significant cytotoxicity against three different cell lines in culture with IC50 values of aroimd 0.25 pg/mL [55]. Lamellarins K and L... 

Pla, D., Mardial, A., Olsen, C.A., Francesch, A., Cuevas, C Alberido, F., and Ivarez, M. (2006) Synthesis and stmcture-activity relationship study of potent cytotoxic analogues of the marine alkaloid lamellarin D. J. Med. Chem., 49, 3257—3268. 

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