Netamines H–N, Tricyclic Alkaloids from the Marine Sponge Biemna laboutei and Their Antimalarial Activity

Abstract

Chemical examination of the CH2Cl2-MeOH (1:1) extract of the Madagascar sponge Biemna laboutei resulted in the isolation of seven new tricyclic alkaloids, netamines H-N (1-7), along with the known netamine G and mirabilins A, C, and F. Their structures were elucidated by interpretation of 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their cytotoxicity against KB cells and their antiplasmodial activity. Netamine M (6) was found to be cytotoxic, with an IC50 value in the micromolar range, and netamine K (4) exhibited activity against Plasmodium falciparum with an IC50 value of 2.4 μM.

Chemical and Biological Aspects of Marine Sponges from the Family Mycalidae

“…This is the only report of guanidine tricyclic alkaloids from a member of the family Mycalidae. Several of these mirabilins have since been reported in other sponge species including mirabilins A (84), C (86), and F (89) from Biemna laboutei [34], a Clathria (Isociella) sp. [35], a Batzella sp.…”

“…Mirabilins are members of a structurally diverse class of compounds that have been reported in a range of taxa, including both marine and terrestrial microorganisms, invertebrates, and plants (see [39] and previous reviews in series). Related tricyclic alkaloids with a guanidine moiety have been reported in five other sponge genera including Acanthella [40], Batzella [34,36,41], Clathria (Isociella) [35,42], Monanchora [37,38,43,44], and Ptilocaulis [45]. Some of these mirabilins have been reported to possess moderate biological activities.…”

“…Some of these mirabilins have been reported to possess moderate biological activities. Mirabilin A (84) has displayed antimalarial activity against Plasmodium falciparum (IC 50 value of 20.7 µM) [34], and mirabilin B (85) has been reported to have antifungal activity against the strain Cryptococcus neoformans (IC 50 value of 7.0 µg/mL) as well as antiprotozoal activity against Leishmania donovani (IC 50 value of 17 µg/mL) [38]. Other members of this structure class have also displayed antimalarial activity [34] and several have displayed cytotoxicity to tumour cells [34,37,41].…”

Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…As shown in Table 1 and Figure 1, potent (IC 50 < 2 µM) to moderate (IC 50 > 2-10 µM) antimalarial activity was reported for several marine natural products (85)(86)(87)(88)(89)(90)(91)(92)(93)(94), although the mechanism of action for these compounds remained undertermined at the time of publication. Cheng and colleagues reported potent antiplasmodial activity in the peptide actinoramide A (85) isolated from Streptomyces species "in all five (P. falciparum) lines retested" [88].…”

Novel Bioactive Natural Products Isolated from Madagascar Plants and Marine Organisms (2009–2017)

“…Both compounds displayed modest toxicity against brine shrimp, with LD 50 values of 4.4 and 10.9 µM, respectively. 4) Seven new tricyclic alkaloids, netamine H-N (10)(11)(12)(13)(14)(15)(16), along with the four known compounds netamine G and mirabilins A, C, and F were isolated from the DCM/methanol (MeOH) extract of the Madagascar sponge Biemna laboutei. The cytotoxicity of all the compounds against the KB cell line and antiplasmodial activity against P. falciparum strains 3D7 and W2 were evaluated.…”