New 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidinium alkaloids (phloeodictynes) from the New Caledonian shallow-water haplosclerid sponge Oceanapia fistulosa. Structural elucidation from mainly LC-tandem-MS-soft-ionization techniques and discovery of antiplasmodial activity.
We report here on new 6-hydroxy-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidinium alkaloids, belonging to the phloeodictyne family, isolated from the haplosclerid sponge Oceanapia[=Phloeodictyon]fistulosa(Bowerbank, 1873) from New Caledonian shallow waters. Online LC-ESI-MS analysis, coupled to tandem fragmentation experiments on the crude alkaloid mixture, allowed us to clarify their flat structures, including structural isomers. At least 25 different components, of which 17 are new members with variable terminus and length chains, were characterised, besides less abundant analogues bearing a thioethylguanidine side chain. Crude mixtures and HPLC enriched fractions proved active against chloroquine-resistant Plasmodium falciparum, with IC(50) values ranging from 0.6 to 6 microM, while cytotoxicity against human A-549 cell line was low. This makes these alkaloids a good prospect as leads for novel antimalarial agents.
Laboratorio di Chimica Bioorganica, Universita di Trento, I-38050 Povo-Trento, Italy. mancini@science.unitn.it
Ines
I
Mancini
Graziano
G
Guella
Michel
M
Sauvain
Cécile
C
Debitus
Anne-Gaëlle
AG
Duigou
Frédéric
F
Ausseil
Jean-Louis
JL
Menou
Francesco
F
Pietra
D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D015394:Molecular Structure; D009510:New Caledonia; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D011161:Porifera / Q000737:chemistry*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000470:Alkaloids; D000962:Antimalarials; D011726:Pyridinium Compounds; D011758:Pyrroles; D002738:Chloroquine