Abstract:
The present investigation was oriented to the discovery of chemical compounds from the Red Sea sponge Amphimedon sp., as a
source of active agents against Trypanosoma brucei, the causal agent of human sleeping sickness. Dereplication analysis of the
active fraction from Amphimedon sp. using liquid chromatography coupled with high-resolution mass spectrometry revealed the
chemical richness of this sponge with diverse alkaloidal classes such as purine, manzamine, bis-piperidine, and pyridine.
Activity-guided fractionation of the total extract showed the antitrypanosomal activity concentrated in the ethyl acetate fraction
(IC50 = 3.8 μg/ml). In silico modelling was carried out on the dereplicated compounds to provide an insight into their
antitrypanosomal mechanism of action with docking study on eight trypanosomal proteins. Molecular dynamics was run for
the complex of zamamidine D and ornithine decarboxylase, which illustrated that zamamidine D has the highest affinity to the
ornithine decarboxylase enzyme. These results highlight the valuable chemical profile of Amphimedon sp., as a lead source for
antitrypanosomal natural products.
