Batzelladines F−I, Novel Alkaloids from the Sponge Batzella sp.:  Inducers of p56^lck-CD4 Dissociation

Abstract

The sponge Batzella sp. from Jamaica contains four new alkaloids, batzelladines F−I (1-4), that induce the p56lck−CD4 dissociation. Batzelladines F−I were isolated using a bioassay-directed fractionation scheme and were identified by interpretation of spectroscopic data. Batzelladines F, G, and H + I were active in the p56lck−CD4 dissociation assay at micromolar concentrations.

Guanidine alkaloid analogs as inhibitors of HIV-1 Nef interactions with p53, actin, and p56 lck

“…Next, we sought to determine whether the in vitro Nef assays reported here could be used to identify small molecules capable of disrupting Nef binding activities. Batzellidine and crambescidin alkaloids quickly became the focus of our efforts because of the known abilities for some batzellidine and crambescidin derivatives to disrupt other protein-protein interactions, including CD4 binding to p56 lck (29,30,32). Competition-binding data demonstrate inhibition of three Nef-ligand interactions by batzellidine and crambescidin analogs (Fig.…”

“…Various batzellidine and crambescidin alkaloids have been reported to inhibit gp120-CD4, CD4-p56 lck , and HIV-1 cellfusion protein-protein interactions (29)(30)(31)(32)(33). With the planar guanidine functionality surrounded by hydrophobic rings, molecules of this class are ideally suited to disrupt the large, relatively flat surfaces common to protein-protein interactions.…”

“…Guanidine alkaloids of the batzelladine family, which were isolated from the sponge Crambe crambe, can inhibit gp120-CD4 binding and induce CD4-p56 lck dissociation (29)(30)(31). Crambescidin guanidine alkaloids from the same sponge have also been shown to inhibit HIV-1 cell fusion (32,33).…”

Crystallographic and NMR studies of antiinfective tricyclic guanidine alkaloids from the sponge Monanchora unguifera

“…1 Members of this class include the series called ptilocaulins, [2][3][4][5] crambescins (crambines), [6][7][8][9] ptilomycalin A, crambescidins, [9][10][11][12][13][14][15] and batzelladines. [15][16][17] They were isolated separately from marine sponges belonging to the genera Batzella, Monanchora, Arenochalina, and Crambe (Order Poecilosclerida) and Ptilocaulis (Order Axinellida) and starfish Fromia monilis, and Celerina heffernani. 18 These metabolites display diverse biological activities including cytotoxicity against P388, L1210, HCT-16, KB cell lines, 2,[10][11][12]14 antifungal activity against Candida albicans, 10 antiviral activity against Herpes simplex virus type 1 (HSV-1), and Hepatitis-B virus [10][11][12][13] and potent calcium channel antagonist activity.…”

Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal and anti-HIV activities

“…Batzelladines A-N, isolated from various sponges of the genus Batzella are of biological interests [7][8][9][10][11]. Batzelladines A and B were found to inhibit the binding of HIV glycoprotein gp-120 to CD4 receptors [7].…”