In the search for new antimalarials, we used the quinone scaffold of marine secondary metabolites as a chemical starting point to synthesize new thiazinoquinone compounds. Most of synthetic derivatives have shown a significant pharmacological activity and some structural requirements, critical for both the antiplasmodial effect and cytotoxicity, have been evidenced. The redox properties of the prepared compounds have been investigated by computational studies and electrochemical assays, which indicated that a higher antiplasmodial activity of some thiazinoquinones is related to their greater ability to form the semiquinone species and strongly interact with free Fe(III)-protoporphyrin IX

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The present work deals with the synthesis of the 10-oxabicyclo[5.2.1]decane framework present in bioactive natural products like physalins, with potential as antitumor agents. This synthetic methodology involves several key reactions: (a) synthesis of polyfunctionalized cycloheptenones by [4 + 3] cycloaddition reactions of furan precursors with oxyallyl cations; (b) Nicholas reaction with propargyl cations stabilized as dicobalt hexacarbonyl complexes; (c) demetallation and hydration of the resulting acetylenes; (d) stereoconvergent aldol cyclization to generate a key oxatricyclic intermediate and (e) a β-fragmentation process that affords, under hypoiodite photolysis, the desired product with moderate to good yield. The final compounds are the result of a radicalary β-fragmentation at the level of C2-C6 with respect to the tertiary hydroxyl group on C6, with an unexpected contraction from a ten- to a nine-membered ring system, via a radical addition to the carbonyl group on C4. The synthetic methodology has been scaled up to multigram level with good overall yield. Further biological, biochemical and biophysical studies are being carried out in our laboratory on these 1,7-epoxycyclononane derivatives to determine the potential of this kind of oxabicyclic compound as future hits and/or leads for the development of new anticancer drugs. The preliminary evaluation of the anticancer activity of the representative synthesized compounds, against the leukaemia cancer cell lines K-562 and SR, shows a promising activity with a GI = 0.01 μM and a LC = 7.4 μM for a conveniently functionalized 10-oxabicyclo[5.2.1]decane.