Lamellarins structure-activity

Figure 15. Structural elements that affect lamellarin biological activities.

Marco, E., Laine, W., Tardy, C., Lansiaux, A., Iwao, M., Ishibashi, F., Bailly, C., Gago, F., (2005). Molecular determinants of topoisomerase I poisoning by lamellarins comparison with camptothecin and structure -activity relationships, J. Med. Chem. 48, 3796-3807. 

Ishibashi, F., Tanabe, S., Oda, T, and Iwao, M. (2002) Synthesis and structure-activity relationships study of lamellarin derivatives. J. Nat. Prod., 65, 500-504. 

The lamellarins constitute an important group of natural products isolated from marine invertebrates such as sponges, molluscs and tunicates with structures without precedents in natural or synthetic compounds. They are characterized for possessing important biological activities. The aim of this review is to provide an overview of the work published since the isolation of the first group of lamellarins <85JA5492> from the marine prosobranch mollusc Lamellaria sp, imtil the beginning of 2004. 

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. 

With more than 350 original structures, almost all of which contain nitrogen, Didemnidae may be regarded as the richest family of the class Ascidiacea, with several molecules that are undergoing clinical trials for their antiviral and anti-tumor activity. Most of the structures isolated from Didemnidae derive from only three genera, Didemnum, Trididemnum and Lissoclinum, which each contain families of active substances (didemnins, eudis-tomins, lamellarins, lissoclinamides and Hssodimides). Table 28.3 shows the main types of structure encountered in the main genera of the order. 

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). 

---