Federica Bianchi

Halogenation of a capsaicin analogue leads to novel vanilloid TRPV1 receptor antagonists

The C‐5 halogenation of the vanillyl moiety of resiniferatoxin, an ultrapotent agonist of vanilloid TRPV1 receptors, results in a potent antagonist for these receptors. Here, we have synthesized a series of halogenated derivatives of ‘synthetic capsaicin’ (nonanoyl vanillamide=nordihydrocapsaicin) differing for the nature (iodine, bromine–chlorine) and the regiochemistry (C‐5, C‐6) of the halogenation. The activity of these compounds was investigated on recombinant human TRPV1 receptors overexpressed in HEK‐293 cells. None of the six compounds exerted any significant agonist activity, as assessed by measuring their effect on TRPV1‐mediated calcium mobilization. Instead, all compounds antagonized, to various extents, the effect of capsaicin in this assay. All 6‐halo‐nordihydrocapsaicins behaved as competitive antagonists against human TRPV1 according to the corresponding Schilds plots, and were more potent than the corresponding 5‐halogenated analogues. The iodo‐derivatives were more potent than the bromo‐ and chloro‐derivatives. Using human recombinant TRPV1, 6‐iodo‐nordihydrocapsaicin (IC50=10 nM against 100 nM capsaicin) was about four times more potent than the prototypical TRPV1 antagonist, capsazepine, and was tested against capsaicin also on native TRPV1 in: (i) rat dorsal root ganglion neurons in culture; (ii) guinea‐pig urinary bladder; and (iii) guinea‐pig bronchi. In all cases, except for the guinea‐pig bronchi, the compound was significantly more potent than capsazepine as a TRPV1 antagonist. In conclusion, 6‐iodo‐nordihydrocapsaicin, a stable and easily prepared compound, is a potent TRPV1 antagonist and a convenient replacement for capsazepine in most of the in vitro preparations currently used to assess the activity of putative vanilloid receptor agonists.

Antioxidant activity of oligomeric acylphloroglucinols from Myrtus communis L

The use of myrtle (Myrtus communis L.) as a culinary spice and as a flavoring agent for alcoholic beverages is widespread in the Mediterranean area, and especially in Sardinia. Myrtle contains unique oligomeric non-prenylated acylphloroglucinols, whose antioxidant activity was investigated in various systems. Both semimyrtucommulone (1) and myrtucommulone A (2) showed powerful antioxidant properties, protecting linoleic acid against free radical attack in simple in vitro systems, inhibiting its autoxidation and its FeCl3- and EDTA-mediated oxidation. While both compounds lacked pro-oxidant activity, semimyrtucommulone was more powerful than myrtucommulone A, and was further evaluated in rat liver homogenates for activity against lipid peroxidation induced by ferric-nitrilotriacetate, and in cell cultures for cytotoxicity and the inhibition of TBH- or FeCl3-induced oxidation. The results of these studies established semimyrtucommulone as a novel dietary antioxidant lead.

Pterocarpans from Bituminaria morisiana and Bituminaria bituminosa.

The aerial parts of Mediterranean papilionaceous plants Bituminaria morisiana and B. bituminosa afforded, along with known phenolics, the prenylated pterocarpans bitucarpin A and B, whose structure was elucidated by spectroscopic techniques. A known isoflavonoid (8-prenyldaidzein) was also obtained for the first time as a genuine plant constituent. The accumulation of pterocarpans at the expense of biogenetically more primitive shikimate metabolites like furanocoumarins or isoflavonoids supports the inclusion of this plant, once part of the genus Psoralea, into the distinct genus Bituminaria.

Corrigendum to Halogenation of a capsaicin analogue leads to novel vanilloid TRPVI receptor antagonists

British Journal of Pharmacology (2003) 140, 1008. doi:10.1038/sj.bjp.0705565