Netamines O–S, Five New Tricyclic Guanidine Alkaloids from the Madagascar Sponge Biemna laboutei, and Their Antimalarial Activities

Abstract

In our continuing program to isolate new compounds from the Madagascar sponge Biemna laboutei, five new tricyclic guanidine alkaloids, netamines O - S (1-5, resp.), have been identified together with the known compounds netamine E (6) and mirabilin J (7). The structures of all new netamines were assigned on the basis of spectroscopic analyses. Their relative configurations were established by analysis of ROESY data and comparison with literature data. Netamines O, P, and Q, which were isolated in sufficient quantities, were tested for their cytotoxic activities against KB cells and their activities against the malaria parasite Plasmodium falciparum. Netamines O and Q were found to be moderately cytotoxic. Netamines O, P, and Q exhibited antiplasmodial activities with IC₅₀ values of 16.99 ± 4.12, 32.62 ± 3.44, and 8.37 ± 1.35 μM, respectively.

Marine natural products

“…630 Both compounds induced similar levels of cellular differentiation of human leukaemia tumour cells to normal erythrocytes at similar levels (ng mL À1 ) to doxorubicin. 631 Guanidine-type alkaloids have been isolated from Biemna laboutei 926-930, 632 Pseudoaxinella reticulata 931-934, 633 Monanchora arbuscula 935-940 (the synthesis of 935 was also achieved), 634 650 Puupehenol 996 (Dactylospongia sp.) exhibited pronounced anti-inammatory activity.…”

Marine alkaloids as bioactive agents against protozoal neglected tropical diseases and malaria

“…Both showed promising antimalarial activity with IC 50 values of 2.4 and 21.0 mM respectively. 81 Three related 83 The bioactivities of this family show high sensitivity to the nature of the various sidechains, and extent of oxidation of the pyrimidine core. Nortopsentin A ( 103) is a structurally distinct bis-(indolyl) imidazole alkaloid found in the sponge Sponhosorites sp., which displayed antimalarial activity against chloroquine-resistant P. falciparum with an IC 50 value of 0.4 mM, resulting in a selectivity index of 14; 84 other marine-derived alkaloids studied in this work showed tenfold reduced activity.…”

Promising antiparasitic agents from marine sponges

“…contortus 6-N-acyladenine alkaloid, phorioadenine A Alkaloid LD99 31 μg/mL*** Phoriospongia sp. Australia ( Farrugia et al, 2014 ) P. falciparum Sesquiterpene isonitrile 7,20-diisocyanoadociane Isonitriles 0.013 μM* Cymbastela hooperi – ( Young et al, 2015 ) 3D7 P. falciparum isocyanide amphilectane-type diterpenes monamphilectines B isocyanide amphilectane-type diterpenes 0.044 μM* Svenzea flava Caribbean Sea ( Avilés et al, 2015 ) isocyanide amphilectane-type diterpenes monamphilectines C 0.043 μM* T. cruzi trypomastigotes Monalidine A Guanidine and Pyrimidine Alkaloids 8 μM** Monanchoraarbuscula Brazil ( Santos et al, 2015 ) Batzelladine D 64 μM*** Batzelladines F 5 μM** Batzelladines L 2 μM** Norbatzelladine L 7 μM** L. infantum promastigotes Monalidine A 2 μM** Batzelladine D 2 μM** Batzelladines F 4 μM** Batzelladines L 2 μM** Norbatzelladine L 2 μM** P. falciparum Netamines O Tricyclic Guanidine Alkaloids 16.99 μM** Biemna laboutei Madagascar ( Gros et al, 2015 ) Netamines P 32.62 μM*** Netamines Q 8.37 μM** 3D7 P. falciparum sulfated polysaccharides sulfated polysaccharides 66.3 μg/ml*** Desmapsamma anchorata …”