Iodinated Meroditerpenes from a Red Alga Callophycus sp.

Abstract

Unique iodine-containing meroditerpenes io-docallophycoic acid A (1) and iodocallophycols A–D (2–5) were discovered from the Fijian red alga Callophycus sp. Because flexibility of the molecular skeleton impaired full characterization of relative stereochemistries by NMR spectroscopy, a DFT-based theoretical model was developed to derive relevant interproton distances which were compared to those calculated from NOE measurements, yielding the relative stereochemistries. The correct 2S,6S,7S,10S,14S enantiomers were then identified by comparison of theoretical and experimental ECD spectra. Biological activities of these iodinated and brominated meroditerpenes and additional new, related bromophycoic acid F (6) and bromophycoic acid A methyl ester (7), were evaluated for relevant human disease targets. Iodocallophycoic acid A (1) showed moderate antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF) with MIC values of 1.4 and 2.2 μg mL−1, respectively. It also potentiated the anti-MRSA activity of oxacillin in a synergistic fashion, resulting in an 8-fold increase in oxacillin potency, for a MIC of 16 μg mL−1.

Marine natural products

“…are unique meroditerpenes since they contain both iodine and bromine. 390 The compounds contain two polysubstituted cyclohexyl groups bridged by a exible ethyl linker and because of this, the determination of their relative conguration proved challenging. The problem was solved through the development of a DFT model to predict inter proton distances and these were then compared to distances calculated from NOEs.…”

“…The alga also contained bromophycoic acid F 946 and bromophycoic acid A methyl ester 947. 390 New polyether triterpenes intricatriol 948 (Laurencia sp.) 380 and alfredensinols A-C 949-951 (L. alfredensis) 389 were reported.…”

Isolation and Potential Biological Applications of Haloaryl Secondary Metabolites from Macroalgae

“…In 2017, four new iodinated and brominated meroditerpenes (iodocallophycols A to D, 19–22 ) with a unique structure were discovered from the Fijian red alga Callophycus sp. by Lavoie et al ( Figure 3 , Supplementary Table S1 ) [ 3 ]. At 10 µM, none of the compounds revealed antibiotic activity against several wild-type and resistant bacterial strains [ 3 ].…”

“…Interestingly, the number of secondary metabolites with chlorine is very similar to that with iodine, which would not be expected because chloride and bromide are much more abundant than iodide in seawater [ 1 ]. According to Lavoie et al (2017), this disproportionately high number of iodinated compounds can be explained by the higher oxidation potential of iodide compared to bromide and chloride, allowing its faster oxidation by haloperoxidases, and their incorporation into the biosynthetic pathway of the secondary metabolites [ 2 , 3 ]. It is noteworthy that the halogenation degree is relatively higher for brominated metabolites than for chlorinated and iodinated metabolites ( Table 1 ).…”

Antibacterial Oligomeric Polyphenols from the Green Alga Cladophora socialis

“…Other red algae produce a variety of structurally simple, often halogenated phenolics of mostly unknown biological function, 9 although more complex, aromatic natural products of mixed shikimate and isoprenoid biosynthetic origin have also been observed. 10 Many members of the brown algae (phylum Ochrophyta), which evolutionarily diverged just before land plants, produce polymeric, acetogenic, phenolic compounds (phlorotannins) constituting 1–20% of dry mass. 11 These oligomers of phloroglucinol protect tissues against UV radiation and herbivory 11,12 and may contribute to structural support.…”