This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included.

Environmental context: The general perception that nature does not produce compounds containing halogens – chlorine, bromine, iodine and fluorine – is now known to be erroneous. Modern isolation and identification techniques have led to the discovery of more than 5000 halogen-containing compounds from myriad marine and terrestrial plant and animal sources. Many of these compounds possess extraordinary biological activity, including anticancer, antiviral and antibacterial activity of potential human benefit. This short review presents the naturally occurring organohalogen compounds discovered and characterised in 2014. They include compounds from both marine and terrestrial organisms, such as algae, sponges, corals, tunicates, bryozoans, fungi, bacteria, cyanobacteria and plants. Several novel structural types have been characterised. From only ~24 in 1968, naturally occurring organohalogens currently number more than 5000, and they continue to be discovered in all regions of the world. This review presents the 114 discovered organohalogens from natural sources in the year 2014.

A novel synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), previously reported to have potent differentiating, antiproliferative, and antiinflammatory activities, has been identified as a ligand for the peroxisome proliferator-activated receptor γ (PPARγ). CDDO induces adipocytic differentiation in 3T3-L1 cells, although it is not as potent as the full agonist of PPARγ, rosiglitazone. Binding studies of CDDO to PPARγ using a scintillation proximity assay give a Ki between 10−8 to 10−7m. In transactivation assays, CDDO is a partial agonist for PPARγ. The methyl ester of CDDO, CDDO-Me, binds to PPARγ with similar affinity, but is an antagonist. Like other PPARγ ligands, CDDO synergizes with a retinoid X receptor (RXR)-specific ligand to induce 3T3-L1 differentiation, while CDDO-Me is an antagonist in this assay. The partial agonism of CDDO and the antagonism of CDDO-Me reflect the differences in their capacity to recruit or displace cofactors of transcriptional regulation; CDDO and rosiglitazone both release the nuclear receptor corepressor, NCoR, from PPARγ, while CDDO-Me does not. The differences between CDDO and rosiglitazone as either partial or full agonists, respectively, are seen in the weaker ability of CDDO to recruit the coactivator CREB-binding protein, CBP, to PPARγ. Our results establish the triterpenoid CDDO as a member of a new class of PPARγ ligands.