Lamellarins inhibition

Baimbaek, D., Trinkler, N., Ferandin, Y., Lozach, O., Ploypradith, P., Rucirawat, S., Ishibashi, F., Iwao, M., Meijer, L., (2008). Anticancer Alkaloid Lamellarins Inhibit Protein Kinases, Mar. Drugs 6, 514-527. 

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>. 

Lamellarin a 20-sulfate inhibits integrase terminal cleavage activity with an IC50 of 16 pM and strand transfer activity with an IC50 of 16 pM and possesses a low toxicity with an LD50 of 274 pM whereas other sulfated lamellarins (lamellarin U 20-sulfate and lamellarin V 20-sulfate) were toxic in the 100 pM range and lamellarins T and N without the sulfate ester were more toxic. The site of action of lamellarin a 20-sulfate was mapped and it was postulated that it binds to a site composed of multiple integrase domains. 

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... 

Ballot C, Kuza J, Lancel S, Martoriati A, Hassoun SM, Mortier L, et al. Inhibition of mitochondrial respiration mediates apoptosis induced by the antitumoral alkaloid lamellarin D. Apoptosis 2010 15(7) 769-81. 

C. Ballot, A. Martoriati, M. Jendoubi, S. Buche, P. Formstecher, L. Mortier, J. Kluza, and P. Marchetti, Another facet to the anticancer response to lamellarin D induction of cellular senescence through inhibition of topoisomerase 1 and intracellular Ros production. Afor. Drugs, 12 (2014) 779-98. 

Indolizine is the core structure of many of the naturally occurring alkaloids such as swainso-nine (a potent inhibitor of Golgi alpha-mannosidase II, an immunomodulator and a potential chemotherapy drug), monomorine (might be used to lure ants to their doom), gephyrotoxin (muscarinic antagonist), and lamellarins (HIV-1 integrase inhibition and antibiotic activity) [6]. 

The pyrrole nucleus is the characteristic structural motif of numerous natural (stor-niamide A, lamellarin P, marinopyrrole B) and synthetic products [24], Many poly-functionalized pyrroles are known to display interesting biological activities [25], In addition, pyrroles were observed to inhibit cytokine-mediated diseases and were also found to have some apphcations in materials chemistry [26], The growing importance and wide usefiilness of polysubstituted pyrroles have kept in focus the search for new methods for the efficient synthesis of these heterocycles. 

The intertidal limpet Collisella limatula contains limatulone (914) which inhibits fish and crab predation (600b). Food pellets containing 914 at levels of 0.05% dry weight or more induced regurgitation in the intertidal fish Gibbonsia elegans, a known limped predator. The marine prosobranch mollusc, Lamellaria sp. furnished four aromatic metabolites, lamellarins A-D (915-918) (600 c). At concentrations of 19 pg/mL, 918 caused a 78% inhibition of cell division in the fertilized sea urchin egg assay while 917 caused 15% inhibition and 915 as well as 916 were inactive. 

Isolated more recently from Dendrilla nigra collected in Saipan (Mariana Islands), neolamellarins A and B and other related molecules differ from lamellarins in the absence of the carboxylic acid group at position 2 on the pyrrole nucleus. Most of these derivatives inhibit HIF-1 (Liu et al., 2007). 

---