Giuseppina Cioffi

Secondary metabolites from the aerial parts of Salvia palaestina Bentham

Three sesterterpenes (1-3), one triterpene (4) and five diterpenes (5-9) were isolated from the aerial parts of Salvia palaestina Bentham (Lamiaceae), together with two sesquiterpenes, 10 known diterpenes, three triterpenes, and rosmarinic acid. Their structural elucidation was accomplished by extensive spectroscopic methods including 1D ((1)H, (13)C, (13)C DEPT, TOCSY, NOESY) and 2D NMR experiments (DQF-COSY, HSQC, HMBC, ROESY) as well as ESIMS analysis and chemical analysis.

Antiproliferative oleanane saponins from Meryta denhamii.

Eight new oleanane saponins (1- 8) together with four know saponins (9-12) were isolated from the aerial parts of Meryta denhamii. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The antiproliferative activity of all compounds was evaluated using three murine and human cancer cell lines: J774.A1, HEK-293, and WEHI-164.

Antioxidant Bibenzyl Derivatives from Notholaena nivea Desv.

Four new bibenzyl derivatives were isolated, together with other known bibenzyls, by bioassay-guided fractionation of a CHCl3-MeOH extract of Notholaena nivea Desv. (Pteridaceae) aerial parts. The structures were elucidated by NMR, ESIMS and other spectral analyses. Their antioxidative effects towards superoxide, lipidic peroxidation and the 2,2’-azino-bis-3-ethilbenzothiazoline-6-sulfonic acid (ABTS) radical were assayed. Results showed that the compound 3,12-dihydroxy-5-methoxybibenzyl (6) is the most active compound in the ABTS free-radical scavenging test, while in the coupled oxidation of β-carotene and linoleic acid assay the compound 5,12-dihydroxy-3-methoxydibenzyl-6-carboxylic acid (1) exerted the highest activity after 1h. A superoxide anion enzymatic test was also carried out and the results were confirmed by an inhibition of xanthine oxidase activity assay. The putative protective role played by compounds 1 and 6 on the injurious effects of reactive oxygen metabolites on the intestinal epithelium, using a Caco-2 human cell line, was investigated. H2O2-induced alterations were prevented by preincubating the cells with compounds 1 and 6.

A New Series of 1,3-Dihidro-Imidazo[1,5-c]thiazole-5,7-Dione Derivatives: Synthesis and Interaction with Aβ(25-35) Amyloid Peptide

Deposition of senile plaques composed of fibrillar aggregates of Aβ‐amyloid peptide is a characteristic hallmark of Alzheimer’s disease. A widely employed approach in the study of anti‐Alzheimer agents involves the identification of substances able to prevent amyloid aggregation, or to disaggregate the amyloid fibrils through a direct structural interaction with the soluble or aggregated forms of the peptide. Here, we report the synthesis of a set of 1,3‐dihydro‐3,6‐disubstituted‐imidazo[1,5‐c]thiazole‐5,7‐dione derivatives supporting different alkyl, aryl and alkylamine side chains. The ability of these compounds to interact with the Aβ(25‐35) peptide was evaluated using circular dichroism, nuclear magnetic resonance and thioflavin fluorescence spectroscopy. A molecular model for Aβ(25‐35)–ligand interactions was calculated by molecular docking procedures. Our data show that the ability of the synthesized compounds to modify the structural behaviour of Aβ(25‐35) varies as a function of the overall structural features of the ligands rather contributions from specific individual substituents.

Antioxidant activity of thioureidic derivatives I

Recent developments in biomedical science have shown that free radicals are involved in many diseases. They attack the unsaturated fatty acids in the biomembrane resulting in membrane lipid peroxidation, which is strongly connected to aging, carcinogenesis and atherosclerosis. Free radicals also attack DNA and cause mutation leading to cancer. In addition lipid peroxidation is an important factor of deterioration in the processing and storage of food. Therefore, it is important to search for new effective radical scavengers (Sci. Rev. 2 (1997) 152; J. Nat. Prod. Rev. 63 (2000) 1035). In this manuscript we describe the antioxidant activity of new thioureidic compounds.

Steroids from Vernonia nigritiana Oliv. & Hiern. with topical anti-inflammatory activity

Vernonia nigritiana Oliv. & Hiern. (Asteraceae) is a widely distributed plant of West Africa where is traditionally used against dermatoses, digestive insufficiency, fever, rheumatism and headache [1]. Previous studies revealed a topical anti-inflammatory activity of a chloroform extract from the aerial parts of V. nigritiana, containing stigmastane-type steroids [2]. Continuing the investigation of V. nigritiana constituents, nine polyhydroxylated stigmasterol glycosides (1-9) and six (10-15) polyhydroxylated stigmastanes having a Δ7(8), 9(11), 24(28) -steroid cyclic system, were isolated. Their structure was elucidated by NMR, 1D-TOCSY, 2D-HOHAHA, COSY-DQF, HSQC, HMBC, 1D-ROESY and 1D-NOESY. The molecular formula of the compounds was confirmed by MS analysis. All the compounds were screened for their topical anti-inflammatory activity as inhibition of the Croton oil-induced ear oedema in mice [3]. Each compound provoked a significant oedema reduction, the most active being compounds 1 and 12 (ID50=0.10 and 0.21µmol/cm2, respectively). Their effect was only two and five fold lower than that of the steroidal drug hydrocortisone (ID50=0.04µmol/cm2). Compounds 2-11 and 13-15 provoked inhibitions in the range of 31–83% at the highest dose (0.5µmol/cm2). As reference, the parent compounds stigmasterol and stigmastanol (0.5µmol/cm2) were inactive. To clarify a possible mechanism of action, these compounds were evaluated for their ability to inhibit NF-κB, a transcription factor regulating the expression of inflammatory macromolecules. Studies, carried out in an electrophoretic mobility shift assay [4], showed a complete NF-κB inhibition induced by compounds 1 and 5 (50µM), and a slight inhibition for compounds 6 (50µM) and 8 (20–100µM). References: [1] Igile, G. et al. (1995) J. Nat. Prod. 58: 1438–1443. [2] Cioffi G. et al. (2001) International Symposium of the Phytochemical Society of Europe. Lausanne, 12th-14th September 2001. [3] Tubaro A. et al. (1985) Agents Actions 17: 317–319. [4] Lyss G. et al. (1997) Biol. Chem. 378: 951–961.