Luisella Verotta

Secoiridoids from Olea europaea

Abstract Three new secoiridoids have been isolated from the leaves of Olea europaea along with the previously reported. The compounds were identified by spectral means.

Are acylphloroglucinols lead structures for the treatment of degenerative diseases

In recent years a widespread interest in the antidepressant activity of Hypericum perforatum L. has attracted much activity in investigating metabolites from the Guttiferae, many of which are biologically active compounds with an acylphloroglucinol moiety. A common background in the traditional uses of plants belonging to Guttiferae family is their wound healing properties which has been connected to the established antimicrobial activities of the phloroglucinols present. These metabolites share a common acylated 1,3,5-trihydroxy-benzene core of polyketide origin which undergoes alkylation processes. Polycyclic polyprenylated acylphloroglucinols feature a highly oxygenated and densely substituted bicyclo[3.3.1]nonane-1,3,5-trione core appended with prenyl or geranyl side chains. Secondary cyclizations involve the β-diketone and pendant olefinic groups affording adamantanes, homoadamantanes, dihydrofurano- or pyrano- fused structures. These products are claimed to possess antioxidative, antiviral and antimitotic properties. Increasing interest is related to their function in the CNS as modulators of neurotransmitters associated with neuronal damage and depression.

Antiproliferative Effects on Tumour Cells and Promotion of Keratinocyte Wound Healing by Different Lichen Compounds

Five compounds representative of major structural classes of lichen polyketides, VIZ. (+)-usnic (1), salazinic (2), vulpinic (3), gyrophoric (4), and evernic acids (5), were investigated for their ability to affect cell proliferation or wound healing, two functional targets of relevance for research on cancer or tissue regeneration. The experiments were carried out on MM98 malignant mesothelioma cells, A431 vulvar carcinoma cells, and HaCaT keratinocytes. The NRU and CV cytotoxicity assays showed high toxicity for (+)-usnic acid, intermediate toxicity for vulpinic acid, and low toxicity for salazinic, gyrophoric and evernic acids. Scratch wounding experiments on HaCaT monolayers, in the presence of subtoxic doses of lichen compounds, showed strong wound closure effects by (+)-usnic and gyrophoric acid, an intermediate effect by vulpinic and salazinic acids, and no effect by evernic acid. A combination of (+)-usnic and gyrophoric acids gave a further increase in the wound closure rates. The results of a cell migration test correlated with the wound healing data. In conclusion, (+)-usnic acid might be a particularly interesting compound for the prevention of hyperproliferation syndromes, while (+)-usnic and gyrophoric acids qualify as interesting leads in the promotion of tissue regeneration.

Synthesis and Antinociceptive Activity of Chimonanthines and Pyrrolidinoindoline-Type Alkaloids

Hodgkinsine, a trimeric pyrrolidinoindoline type alkaloid, present as a major constituent of Psychotria spp. (Rubiaceae), has shown to produce dose-dependent, naloxone reversible, analgesic effect in thermal models of nociception and in the capsaicin-induced pain. SAR studies have been initiated by synthesizing the three diastereomeric dimers (chimonanthines) (11-13) which were evaluated in vitro and in vivo along with the synthetic intermediates. Strong binding affinities for mu opioid receptors were found for (-)- and (+)-chimonanthine monourethanes (9 and 10), whereas (-)-, (+)- and (meso)-chimonanthine (11-13) and hodgkinsine displayed low affinity. In vivo data have shown that only (+)-chimonanthine (12) and calycosidine resemble the analgesic profile found for hodgkinsine.

Hyperforin, an anti-inflammatory constituent from St. John's wort, inhibits microsomal prostaglandin E 2 synthase-1 and suppresses prostaglandin E 2 formation in vivo

The acylphloroglucinol hyperforin (Hyp) from St. Johns wort possesses anti-inflammatory and anti-carcinogenic properties which were ascribed among others to the inhibition of 5-lipoxygenase. Here, we investigated whether Hyp also interferes with prostanoid generation in biological systems, particularly with key enzymes participating in prostaglandin (PG)E2 biosynthesis, i.e., cyclooxygenases (COX)-1/2 and microsomal PGE2 synthase (mPGES)-1 which play key roles in inflammation and tumorigenesis. Similar to the mPGES-1 inhibitors MK-886 and MD-52, Hyp significantly suppressed PGE2 formation in whole blood assays starting at 0.03–1 μM, whereas the concomitant generation of COX-derived 12(S)-hydroxy-5-cis-8,10-trans-heptadecatrienoic acid, thromboxane B2, and 6-keto PGF1α was not significantly suppressed up to 30 μM. In cell-free assays, Hyp efficiently blocked the conversion of PGH2 to PGE2 mediated by mPGES-1 (IC50 = 1 μM), and isolated COX enzymes were not (COX-2) or hardly (COX-1) suppressed. Intraperitoneal (i.p.) administration of Hyp (4 mg kg−1) to rats impaired exudate volume and leukocyte numbers in carrageenan-induced pleurisy associated with reduced PGE2 levels, and Hyp (given i.p.) inhibited carrageenan-induced mouse paw edema formation (ED50 = 1 mg kg−1) being superior over indomethacin (ED50 = 5 mg kg−1). We conclude that the suppression of PGE2 biosynthesis in vitro and in vivo by acting on mPGES-1 critically contributes to the anti-inflammatory efficiency of Hyp.

Cycloartane triterpene glycosides from Astragalus trigonus

Three new cycloartane glycosides, trigonoside I, II and III, and the known astragalosides I and II were isolated from the roots of Astragalus trigonus. The structures of the new glycosides were totally elucidated by high field (600 MHz) NMR analyses as cycloastragenol-6-O-beta-xylopyranoside, cycloastragenol-3-O-[alpha-L-arabinopyranosyl(1-->2)-beta-D- xylopyranosyl]- 6-O-beta-D-xylopyranoside and cycloastragenol-3-O-[alpha-L-arabinopyranosyl (1-->2)-beta-D-(3-O-acetyl)-xylopyranosyl]-6-O-beta-D-xylopyranoside.

Polyacetylenes from Sardinian Oenanthe fistulosa: A Molecular Clue to risus sardonicus

An investigation of Oenanthe fistulosa from Sardinia afforded oenanthotoxin (1a) and dihydrooenanthotoxin (1b) from the roots and the diacetylenic epoxydiol 2 from the seeds. The absolute configuration of 1a and 1b was established as R by the modified Mosher’s method, and the structure of 2 by chemical correlation with (+)-(3R,8S)-falcarindiol. Oenanthotoxin (1a) and dihydrooenanthotoxin (1b) were found to potently block GABAergic responses, providing a molecular rationale for the symptoms of poisoning from water-dropwort (Oenanthe crocata) and related plants. These observations bear relevance for a series of historical and ethnopharmacological observations on the identification of the Sardonic herb and the molecular details of the facial muscular contraction caused by its ingestion (risus sardonicus).

Uncovering the Structure of Human Red Hair Pheomelanin: Benzothiazolylthiazinodihydroisoquinolines As Key Building Blocks

Biomimetic oxidation of the pheomelanin precursor 5-S-cysteinyldopa in the presence of Zn(2+) ions led to the isolation of two isomeric products, one of which could be identified as the benzothiazolylthiazinodihydroisoquinoline 5, while the other proved too unstable for a complete characterization. Both these products were converted into more stable oxidized forms, which after ethylchloroformate derivatization were characterized as the ethyl ester/ethoxycarbonyl isoquinolines 8 and 9. Compound 5 exhibited absorption characteristics similar to those of red hair pheomelanin, including a main band around 400 nm in acids. Similarly to red hair pheomelanin and synthetic pigments, 5 afforded on chemical degradation a thiazolylpyridinecarboxylic acid fragment. Model chemical studies allowed the proposal of a formation mechanism for the benzothiazole and dihydroisoquinoline systems in compound 5.

SAPONINS FROM CROSSOPTERYX-FEBRIFUGA

Abstract Two bisdesmosidic saponins from the roots of Crossopteryx febrifuga were isolated by means of reversed phase HPLC. They were characterized on the basis of chemical and spectral data as 3-O-β- d -glucopyranosyl-2β,3β,6β,16α,23-pentahydroxyolean-12-en-28-oic acid 28-O-[α- l -rhamnopyranosyl(1→3)] [β- d -xylopyranosyl-(1→4)] [α- l -rhamnopyranosyl(1→2)]α- l -arabinopyranoside and 3-O-[β- d -apiofuranosyl(1→3)]β- d -glucopyrano-syl-2β,3β,6β,16α,23-pentahydroxyolean-12-en-28-oic acid 28-O-[α- l -rhamnopyranosyl(1→3)] [β- d -xylopyranosyl-(1→4] [α- l -rhamnopyranosyl(1→2)]α- l -arabinopyranoside. 2D NMR experiments were useful in providing complete information on the structure and geometry of the new sapogenin present.

Saponins from Albizzia anthelmintica

Abstract The structures of three new saponins from the bark of Albizzia anthelmintica were established to be 3-O-[β- d -glucopyranosyl(1 → 3)] [α- l -arabinopyranosyl(1 → 2)] [α- l -arabinopyranosyl(1 → 6)] 2-acetamido-2-deoxy-β- d -glucopyranosyl echinocystic acid; 3-O-[α- l -arabinopyranosyl(1 → 2)][α- l -arabinopyranosyl(1 → 6)] 2-acetamido-2-deoxy-β- d -glucopyranosyl echinocystic acid and, present in small amounts, 3-O-[α- l -arabinopyranosyl(1 → 6)] 2-acetamido-2-deoxy-β- d -glucopyranosyl echinocystic acid.