Giuliano Delle Monache

Prenylated Flavonoids: Pharmacology and Biotechnology

Within the flavonoid class of natural products the prenylated sub-class is quite rich in structural variety and pharmacological activity. In the last twenty years a huge number of new structures has been reported, mostly from Leguminosae and Moraceae, with few coming from other genera. The presence, in different forms, of the isoprenoid chain can lead to impressive changes in biological activity, mostly attributed to an increased affinity for biological membranes and to an improved interaction with proteins. Molecules, such as xanthohumol and sophoraflavanone G, while being very structurally simple, show numerous pharmacological applications and are ideal candidates for SAR aimed to the discovery of new drugs. Only recently the biogenesis of these compounds has been more extensively studied and much attention has been focused on the enzymes involved in the modification and transfer of the prenyl unit.

Correlated effects during the bioconversion of waste olive waters by Lentinus edodes

Waste-olive-waters arising from the solid-liquid processing system were degraded in agitated liquid cultures of the white-rot fungus Lentinus edodes. About 45% of biodecolouration and 75% of total organic carbon reduction were achieved within 4 days. Over the same period, the content of total phenols was reduced by 66%. The release of exo-enzymes involved in the metabolism of phenolic compounds (phenol-oxidases and Mnperoxidase) was greatly enhanced with respect to the control. A highly-significant correlation was observed between decolourization, total organic carbon and total phenols.

Two isoflavones and a flavone from the fruits of Maclura pomifera

Abstract Stabilized and optimized cell suspension cultures of Maclura pomifera showed a flavonoid accumulation qualitatively different from that of the intact plant. For a better comparison between in vivo and in vitro production, a re-examination of the fruit extract was undertaken. The study, involving super fluid chromatography, led to the isolation and structure determination of flavonoids not previously reported in the plant. Three of these compounds are new. The presence of flavonoids in stems and leaves was also investigated.

The contribution of oxazolidinone frame to the biological activity of pharmaceutical drugs and natural products.

The development of resistance by the antibiotics in the Gram-positive pathogenic bacteria over the last twenty years and continuing today has created a need for new antibiotic classes, which may be unaffected by existing bacterial resistance. The oxazolidin-2-ones represent not only a new class with a novel mechanism of action, but also satisfy the requirement for overcoming the resistance mechanisms. Both linezolid and eperozolid, the first chemical candidates, arose from the piperazine subclass, with the first one being chosen further development because of its enhanced pharmacokinetic properties. The main attractive traits of the oxazolidinone series has encouraged further work in the area, and the patent literature reveals that extensive chemical investigation is currently being made. The unexpected early resistance development emphasizes the need for further exploration of features of the oxazolidinone to eliminate these deficiencies. Recently, several changes, involving the C5 side chain as well the N-phenyl heterocyclic ring, give promise for such improvement. Oxazolidinone antibacterial agents comprise also ketolides, derivatives of macrolides, such as erythromycin A, with a newly formed carbamate cycle, with a largely unexplored potential. The oxazolidinone nucleus does not appear only in the structures of antimicrobial drugs, but a number of biological activities are connected with frameworks including the oxazolidinone ring. A partial list of these activities comprises enzyme inhibitors, agonists and antagonists, with a particular citation for a new generation of selective monoamino oxidase inhibitors (befloxatone). The oxazolidinone moiety was found in the structure of few biologically active natural products, such as (-)-cytoxazone and streptazolin. Moreover, in some cases the oxazolidinone ring has been chosen for the preparation of isosteric aza analogues of natural compounds (podophyllotoxin, pilocarpine) that can be more easily synthesised and more hardly inactivated. Finally, the participation of oxazolidinone chiral auxiliaries to several syntheses of natural products must be acknowledged.

Prenylated isoflavonoids: Botanical distribution, structures, biological activities and biotechnological studies. An update (1995-2006)

In contrast with the parent class of flavonoids, the distribution of the isoflavonoid class in the plant kingdom is relatively limited, probably owing to the sporadic occurrence of isoflavone synthase. Isoflavonoids have been mostly found in the subfamily Fabaceae/Papilionoideae of the Leguminosae family. Isoprenoid-substituted (also called complex) isoflavonoids are expressed from a smaller number of plants, as a result of the similarly restricted distribution of prenyltransferases (PT-ase). After the reviews of Tanara & Ibrahim (1995), Boland & Donnelly (1997), the Handbook of Flavonoids by Harborne & C ( Handbook of Flavonoids, 1999), and the paper by Harborne and Williams (2000) few other reports concern the distribution and the biological activity of complex isoflavonoids, except a list of isoflavonoids produced from non leguminous plants. This review deals with an update of the literature on isoprenylated isoflavonoids in the years 1995-2006 and is focused on the following highlights. 1. Natural sources of complex isoflavonoids (2000-2006); 2. Chemical structure variety: new entries (2000-2006) 3. Biological activities and a possible structure-activity relationship (1995-2006) 4. In vitro production and microbial metabolism (1995-2006).

Minor xanthones from Rheedia gardneriana

Abstract 8-Deoxygartanin and two new xanthones, 1,5-dihydroxy-6′,6′-dimethyl-2H-pyrano(2′,3′:3,2)-6″,6″-dimethyl-2H-pyrano(2″,3″:6,7)xanthone and 1,5,6-trihydroxy-6′,6′-dimethyl-2H-pyrano(2′,3′:3,2)-7-(3-methylprop-2-enyl)xanthone, have been isolated from the roots of Rheedia gardneriana . The latter of the two new xanthones has been assigned the trivial name 7-prenyljacareubin while the former has the structure erroneously assigned to pyranojacareubin reported from Garcinia densivenia . The correct identity of the G. densivenia xanthone has been shown to be rheediaxanthone-A.

Prenylated benzophenones from Clusia sandiensis

Abstract From an extract of fruits of Clusia sandiensis the known clusiaphenone A and the new clusiaphenone B (2,4,6-trihydroxy-3,5-diisopentenylbenzophenone) were isolated. Moreover, the structure of machuone, a new polyisoprenylated modified benzophenone, has been determined on the basis of high field 2D NMR techniques. The keto-enolic equilibrium of clusianone, also isolated from the extract, was studied by examination of its 1 H and 13 C NMR spectra.

Filifolinol, a rearranged geranyl aromatic derivative from the resinous exudate of Heliotropium filifolium

Abstract The resinous exudate of Heliotropium filifolium has yielded a new rearranged geranyl aromatic derivative. This result is in agreement with the botanical affinity of some members of the Cochranea section of Heliotropium .

Thymol derivatives from Eupatorium glechonophyllum

Abstract The known 10-acetoxy-8,9-epoxythymolisobutyrate and the new 8,9-dihydroxy-10-acetoxythymolisobutyrate and 8,9,10-trihydroxythymol have been isolated from the thallus of Eupatorium glechonophyllum . The acetonide of the last compound was also obtained. The possibility that the new compounds are artefacts is discussed.

Chalcone dimethylallyltransferase from Morus nigra cell cultures. Substrate specificity studies.

A new prenyltransferase (PT) enzyme derived from the microsomal fractions of cell cultures of Morus nigra was shown to be able to prenylate exclusively chalcones with a 2′,4′‐dihydroxy substitution and the isoflavone genistein. Computational studies were performed to shed some light on the relationship between the structure of the substrate and the enzymatic activity. PT requires divalent cations, particularly Mg2+, to be effective. The apparent K m values for γ,γ‐dimethylallyldiphosphate and 2′,4′‐dihydroxychalcone were 63 and 142 μM, respectively. The maximum activity of the enzyme was expressed during the first 10 days of cell growth.