Peroxyplakoric acid

Some 1,2-dioxanes and 1,2-dioxolanes derivatives such as the two diastereomers of methyl esters of peroxyplakoric acid (A3 and B3) (85) isolated from marine sponges Plakortis sp., have proven to possess good antimalarial activity, with IC50 values of about 50 ng/mL for both compounds. Furthermore, a polyether (86) recently isolated from marine Streptomyces sp. H668 also displayed a useable antimalarial activity, with an IC50 value of about 150 ng/mL. ... 

Fig. (21) Chemical structures of peroxyplakoric acids A3 (57) and B3 (58) methyl esters...

The methyl esters of peroxyplakoric acids A3 (57) [Fig. (21)] and B3 (58) [Fig. (21)], isolated from Plakortis sp., showed a very good antimalarial activity against P. falciparum with IC50 = 50 ng/mL and a good selective toxicity index (about 200) [78]. Through the syntheses of some analogues of these active compounds, some conclusions about the structural requirements within these classes of antimalarials were drawn. For example, compound 59 [Fig. (22)] proved to be almost completely inactive, whereas compound 60 [Fig. (22)] retained the in vitro activity of peroxyplakoric acid B3 methyl ester, indicating the importance of the side chain for the antimalarial activity [79]. 

Fig. (22) Two synthetic analogues of peroxyplakoric acids methyl esters.

Finally, the low antimalarial activity observed for two additional marine cycloperoxides strictly related to peroxyplakoric acid B3 methyl ester, namely chondrillin, (61) [Fig. (23)] [81], and muqubilone, (62) [Fig. (23)] [82], provides other interesting suggestions. The insertion of a double bond within the 1,2-dioxane ring is evidently detrimental for the activity, while the presence of the methoxy group at C-3 exerts a pivotal role in the determination of the antimalarial activity for this group of molecules. Most likely, simple 1,2-dioxane molecules, that, like plakortin, are consistently active, possess other features that are able to compensate the lack of the methoxy group. 

Cyclic peroxides Plakortis sp. Peroxyplakoric acid Al methyl ester (8), and Bl methyl ester [56]... 

Peroxyachipendole, P-20071 10,12-Peroxycalamenene, see E-30021 Peroxyplakoric acid A, P-20072 Peroxyplakoric acid A2, in P-20072 Peroxyplakoric acid A3, P-20073 Peroxyplakoric acid B, in P-20072 Peroxyplakoric acid B3, in P-20073 Perrottetinen, P-30065 Peruvianoside A, P-10084 Perymenic acid, in H-10170 Petalostemumol, see P-30054 Petalostemumol G, see P-30055 Petchicine, P-20074... 

Dihydro-2-methoxy-3,4-dimethyl-5-oxo-2-furannonanoic acid Me ester, in D-30119 Methynolide, in M-10079 Peroxyplakoric acid A3, P-20073 Peroxyplakoric acid B3, in P-20073... 

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