Abstract
Recent developments in marine drug discovery from three South African marine invertebrates, the tube worm Cephalodiscus gilchristi, the ascidian Lissoclinum sp. and the sponge Topsentia pachastrelloides, are presented. Recent reports of the bioactivity and synthesis of the anti-cancer secondary metabolites cephalostatin and mandelalides (from C. gilchristi and Lissoclinum sp., respectively) and various analogues are presented. The threat of drug-resistant pathogens, e.g., methicillin-resistant Staphylococcus aureus (MRSA), is assuming greater global significance, and medicinal chemistry strategies to exploit the potent MRSA PK inhibition, first revealed by two marine secondary metabolites, cis-3,4-dihydrohamacanthin B and bromodeoxytopsentin from T. pachastrelloides, are compared.
Highlights
The plethora of intertidal and subtidal marine organisms inhabiting the ca. 26,000-km coastline of Africa provide a relatively untapped opportunity for the discovery of new bioactive secondary metabolites
Given the global problem of obtaining sufficient supplies of bioactive marine natural products from the ocean for further drug development [4], the bioactive secondary metabolites from these three South African marine invertebrates have been the subject of concerted synthetic programs geared towards producing sufficient amounts of either the natural product or potentially more bioactive analogues, for detailed biological and in vitro studies
The methanolic extract of the South African sponge, Topsentia pachastrelloides (Figure 1c), showed significant activity in the methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase (PK) inhibition assay, and subsequent bioassay-guided fractionation of this extract yielded a cohort of four bisindole alkaloids of which, the two known metabolites cis-3,4-dihydrohamacanthin B (25, Figure 7) and bromodeoxytopsentin (26)
Summary
The plethora of intertidal and subtidal marine organisms inhabiting the ca. 26,000-km coastline of Africa provide a relatively untapped opportunity for the discovery of new bioactive secondary metabolites. McPhail and co-workers reported that the naturally-occurring mandelalides A and B possessed potent cytotoxicity against human NCI-H460 lung cancer cells (IC50 12 and 44 nM, respectively) and Neuro-2A
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