**4.3 Mandelalides**

Mandelalides A-D are macrocyclic polyketides isolated from a new species *Lissoclinum mandelai* in south Africa. Mandelalides are glycosylated polyketides isolated from ascidian *Lissoclinum* (**Figure 2**)*.* Mandelalides A and B show potent cytotoxicity towards, NCI-H460 cells and mouse Neuro-2a neuroblastoma cells. Mandelalides B display potent antifungicidal activity against *Candida albicans* [32]. Isomandelalide A exhibited unexpectedly high level of activity being more potent than mandelalide B. Glycosylated mandelalides A and B are cytotoxic to

**Figure 2.** *Image showing cyanobacterium* Lissoclinum patella.

neuroblastoma cells at low nanomolecular concentrations. New mandelalides G-L isolated allowing the activity of structure activity relationship, comparing the activities of monoscharrides and macrocyclic acylation on biological activity. The structures of Mandelalidea A and B are shown in the figure. Cytotoxic activity of mandelalide A was dependent on cell density with actively proliferating tumor cells at low density being actively resistant to the compound. Mandelalides A and B inhibited mitochondrial function and induce caspase dependent apoptotic cell death, due to the inhibition of the mammalian ATP synthase complex V at concentrations of 30-100 nM [33]. Cells with oxidative phenotype, was more likely to be inhibited. Cancer cells can shift their mechanism of ATP production from oxidative phosphorylation to Aerobic glycolysis as nutrients become depleted, causing cell death.
