Corrado Tringali

Bioactive compounds from natural sources: isolation, characterisation and biological properties.

Biological Screening Methods in the Search for Pharmacologically Active Natural Products A.J. Vlietinck and S. Apers Applications of Liquid Chromatography/UV/MS and Liquid Chromatography/NMR for the On-line Identification of Plant Metabolites K. Hostettmann and J.L. Wolfender Applications of Modern NMR Techniques in the Structural Elucidation of Bioactive Natural Products P. Neri and C. Tringali Bioactive Secondary Metabolites From Selected Mexican Medicinal Plants: Recent Progress R. Mata, J.F. Rivero-Cruz and D. Chavez Flavonoids as Cancer Chemopreventive Agents L.C. Chang and A.D. Kinghorn Anti-tumor Drugs from the Secondary Metabolites of Higher Plants Y.H. Kuo and M.L. King Bioactive Taxoid Production from Natural Sources M. Jaziri and M. Vanhaelen Anti-HIV Aromatic Compounds from Higher Plants F. De Simone, R. Aquino, N. De Tommasi, N. Mahmood, S. Piacente and C. Pizza Antioxidative Plant Constituents H. Haraguchi Antimalarial Natural Products S. Brogger Christensen and A. Kharazmi Search for Natural Products with Effect on Cyclooxygenase-2 P. Perera, T. Ringbom, U. Huss, M. Vasange and L Bohlin Phytotoxins From Fungi Pathogenic for Agrarian, Forestall and Weedy Plants A. Evidente and A. Motta Limonoids From Meliaceae and their Biological Activities M. Nakatani Glycolipids with Immunomodulating Activity From Marine Sponges V. Constantino, E. Fattorusso and A. Mangoni Metabolites of Marine Opistobranchs: Chemistry and Biological Activity G. Cimino, M.L. Ciavatta, A. Fontana and M. Gavagnin Bioactive Diterpenoids From Japanese Soft Corals K. Yamada and R.. Higuchi

Diterpenes based on the dolabellane skeleton from dictyota dichotoma

From a variety of Dictyota dichotoma we have isolated, in addition to previously reported dolabellane (6-8) and perhydroazulene diterpenes (9,10), four new diterpenoids (2-5). Their structure have been elucidated by spectral analysis and chemical degradation. All the new dolabellane derivatives possess antimicrobial activity against gram-positive and gram-negative organisms.

Natural-derived polyphenols as potential anticancer agents.

In this short review we report selected examples from recent literature to show the potential of natural-derived, low molecular weight polyphenols as antitumor agents. The two major groups of polyphenol analogues have been reviewed here, namely flavonoids and stilbenoids. Notwithstanding these limitations, we listed 75 compounds, many of them representing only the most potent member in a library. In addition, many studies afforded useful SARs which may be the basis for future optimization. In this regard, it is worth highlighting the close structural relationships connecting some families of tubulin inhibitors, namely analogues of chalcones, combretastatin A-4, and resveratrol. Some interesting hybrid molecules have already been obtained, such as chalcone-combretastatin and chalcone-resveratrol hybrids. The optimization of natural polyphenols reputed to be anticarcinogenic has also been addressed to improve their metabolic stability and a number of analogues, which are more stable to metabolic conversion and display comparable or higher antitumor activity than the parent compound, have been obtained. In some cases analogues with higher lipophilicity showed higher activity than the parent compound, in particular stilbenoids, flavanols, and flavone derivatives. Table 1 summarizes the main biological data on the natural-derived polyphenols cited within this review. As a whole, this survey of recently reported, natural-derived polyphenols, though not exhaustive, clearly indicates that intensive research is being carried out in the area of antitumor polyphenol analogues and suggests that in the near future some polyphenolic leads may become useful anticancer drugs or adjuvants in cancer therapy.

Further perhydroazulene diterpenes from marine organisms

3 novel diterpenes,4–6, having the perhydroazulene skeleton already found in pachydictiol A (1) and dictyol A (2) and B (3), have been isolated from both the digestive gland of Aplysia depilans and algae of the family Dictyotaceae.

Chemo-enzymatic preparation of resveratrol derivatives

Abstract Regioselective derivatisation of resveratrol (1) at positions 3, 5 or 4′ was achieved by a chemo-enzymatic procedure based on standard chemical reactions and esterification or alcoholysis in organic solvents catalysed by the commercially available Pseudomonas cepacia (PcL) and Candida antarctica (CaL) lipases.

Antiproliferative Activity of Methylated Analogues of E- and Z-Resveratrol

Abstract The stilbenoids E-resveratrol (E-3,5,4′-trihydroxystilbene, 1), E-3,5,4′-trimethoxystilbene (2), E-3,4,4′-trimethoxystilbene (3) and E-3,4′-dimethoxy-5-hydroxystilbene (4) were converted by photoisomerization to their corresponding Z-isomers 5D8. Compounds 1D8 were subjected to antiproliferative activity bioassays towards a set of four different human cancer cell lines, namely DU-145 (androgen not responsive human prostate tumor), LNCaP (androgen responsive human prostate tumor), M-14 (human melanoma) and KB (human mouth epidermoid carcinoma). The methylated analogues of 1 are more active than the natural lead in the majority of bioassays. The most active compound was Z-3,5,4′-trimethoxystilbene (6), which showed against DU-145 and LNCaP cells GI50 values close to those of the anticancer drug vinorelbine; 6 resulted more active than its E-isomer 2 towards DU-145, LNCaP and especially KB cell lines. A number of methylated Z-isomers displayed a higher activity than their E-isomers, but E-resveratrol (1) was more active than Z-resveratrol (5) towards all the tested cell lines.

Effects of resveratrol analogs on steroidogenesis and mitochondrial function in rat Leydig cells in vitro.

Resveratrol and its analogs are considered to be a promising drug candidate for treatment of cancer and different age‐associated diseases. In the present study we have investigated the effects of resveratrol and its synthetic analogs on steroidogenesis and mitochondrial function in primary cultures of rat Leydig cells. Our findings indicate that resveratrol and its analogs structure‐dependently attenuated hCG‐activated steroidogenesis in Leydig cells through suppression of the expression of steroidogenic acute regulatory protein and cytochrome P450c17. 3,5‐Diacetyl resveratrol was observed to modulate mitochondrial function in Leydig cells, suppressing polarization of inner mitochondrial membrane, and 3,4,4′‐trimethoxystilbene stimulated the overall activity of intracellular reductases involved in the reduction of WST‐1 to formazan. Thus, the inhibitory actions of resveratrol analogs on steroidogenesis in Leydig cells indicate novel mechanisms of action of these compounds, which may be of potential therapeutic interest, where suppression of androgen action is needed. Copyright

Biological effects on granulosa cells of hydroxylated and methylated resveratrol analogues.

Several resveratrol analogues have been designed to improve bioactivity: among these polymethoxystilbenes appear to be particularly promising. The present study was set up to investigate the biological functions of polymethoxystilbenes 2 and 3, recently found in our lab as antiangiogenic agents, on a well-defined swine granulosa cell model. Proliferative activity and effects on steroidogenesis were evaluated, as well as the effect on granulosa cell vascular endothelial growth factor (VEGF) production, since these cells in basic conditions synthesize the main proangiogenic peptide. Moreover, we considered the effect of these two resveratrol analogues on granulosa cell redox status. Analogue 3 inhibited granulosa cell growth, while it stimulated steroidogenesis. A similar effect was displayed by 2 on estradiol 17beta production and cell proliferation at the highest concentration tested. On the other hand, at the same dosage 2 decreased progesterone levels. Both analogues inhibited VEGF output. Granulosa cell redox status was unaffected by resveratrol analogue 2 while the highest concentration of 3 stimulated free radicals generation and scavenging enzyme activities. The overall results indicate that analogue 3 is the more powerful compound, thus suggesting that a slight modification in the structure markedly increases effectiveness. These data could be useful to develop more active resveratrol analogues for therapeutic use.

Identification of the phytotoxin mellein in culture fluids of Phoma tracheiphila

Abstract R-(−)-Mellein was isolated from the organic extract of culture fluids of Phoma tracheiphila, the fungus causing the citrus disease known as m

Structure and conformation of new diterpenes based on the dolabellane skeleton from a Dictyota species

Abstract From the brown alga Dictyota sp. we have isolated three new diterpenes (2,3 and 6) of the dolabellane family. Their structures and conformations have been assigned on the basis of spectral studies, including proton difference decoupling and nuclear Overhauser enhancement difference spectroscopy, and chemical correlation.