Chemical investigations of marine sponges, Axinyssa sp., Petrosia sp. and Cacospongia mycofijiensis

Abstract

Two new nitrogenous germacrane sesquiterpenes, (1Z,4Z)-7alphaH-11-aminogermacra-1(10),4-diene, and N,N'-11-bis[(1Z,4Z)-7alphaH-germacra-1(10),4-dienyl]urea were isolated from the sponge Axinyssa sp., together with a known steroid axinysterol in 0.06, 0.12, and 0.03% w/w based on the MeOH extract, respectively. The compound (1Z,4Z)-7aH-11-aminogermacra-1(10),4-diene showed significant antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, and Candida albicans with inhibition zones of 23, 22, and 27 mm, respectively, at concentration of 500 microgram/disc. The chemical study of the sponge Petrosia sp. led to the isolation of two pyridoacridine alkaloids, including the new 2-bromoamphimedine and the known petrosamine, together with a new isoguanine derivative, namely 1,3,9-trimethyl-8-hydroxyisoguanine in 0.03, 1.5, and 0.01% w/w based on the n-butanol extract, respectively. Petrosamine exhibited antimicrobial activity against Bacillussubtilis with an inhibition zone of 22 mm at concentration of 200 microgram/disc and possessed acetylcholinesterase inhibitory activity with an IC[subscript 50] of 91 nM, which was six times more potent than the reference compound galanthamine. Molecular docking study indicated the quaternary ammonium group of petrosamine donated the major and strong interactions to the key amino acid residues in the active site of Torpedo californica acetylcholinesterase. Bioassay-guided fractionation led to the isolation of the actin polymerization inhibitor latrunculin A and the microtubule-stabilizing agent laulimalide from the sponge, Cacospongia mycofijiensis. The yields of latrunculin A and laulimalide were 0.54 and 0.02% w/w based on the MeOH extract, respectively. In addition, three C1-C14 fragment analogs of laulimalide, LAU13, LAU14, and LAU16, were successfully synthesized in good yields.