Evaluation of flavonoids and furanocoumarins from Citrus bergamia (Bergamot) juice and identification of new compounds.

Bergamot juice (BJ) contains different classes of flavonoids (e.g. flavanones and flavones) that can exert beneficial effects on human health. The aim of this study was to evaluate the qualitative and quantitative composition of a BJ obtained from fruits harvested in Southern Italy (Calabria) at the end of their maturation period. The identity of several flavonoids and furanocoumarins was assessed by co-chromatography, UV spectra and molecular weight comparison. The unknown compounds were dissociated by induced collision (CID-MS) and their identity established through the characteristic ions product. By this approach a complete profile of about twenty compounds (furano-coumarins, flavonoids C- and O-glycosides) present in BJ was obtained. Furthermore, three acylated flavanones, present in amounts of 20.1+/-1.1, 89.3+/-2.2 and 190.1+/-3.1 mg/L, respectively, and which seem to correspond to di-oxalate derivatives of neoeriocitrin, naringin and neohesperidin, were identified for the first time in BJ. The other main flavanones were naringin, neohesperidin and neoeriocitrin, and their content was 167.5+/-1.8, 123.9+/-1.7 and 73.3+/-1.6 mg/L, respectively. Concerning flavones, the total amount in BJ was about 160 mg/L and the main ones were vicenin-2, stellarin-2, rhoifolin and neodiosmin. Bergapten and bergamottin were the primary furanocoumarins in BJ and their amounts were 9.0+/-0.4 and 18.2+/-0.5 mg/L, respectively.

Design and synthesis of phosphonoacetic acid (PPA) ester and amide bioisosters of ribofuranosylnucleoside diphosphates as potential ribonucleotide reductase inhibitors and evaluation of their enzyme inhibitory, cytostatic and antiviral activity.

Continuing our investigations on inhibitors of ribonucleotide reductase (RNR), the crucial enzyme that catalyses the reduction of ribonucleotides to deoxyribonucleotides, we have now prepared and evaluated 5'-phosphonoacetic acid, amide and ester analogues of adenosine, uridine and cytidine with the aim to verify both substrate specificity and contribution to biological activity of diphosphate mimic moieties. A molecular modelling study has been conducted on the RNR R1 subunit, in order to verify the possible interaction of the proposed bioisosteric moieties. The study compounds were finally tested on the recombinant murine RNR showing a degree of inhibition that ranged from 350 microM for the UDP analogue 5'-deoxy-5'-N-(phosphon-acetyl)uridine sodium salt (amide) to 600 microM for the CDP analogue 5'-O-[(diethyl-phosphon)acetyl]cytidine (ester). None of the tested compounds displayed noteworthy cytostatic activity at 100-500 microM concentrations, whereas ADP analogue 5'-N-[(diethyl-phosphon) acetyl]adenosine (amide) and 5'-deoxy-5'-N-(phosphon-acetyl)adenosine sodium salt (amide) showed a moderate inhibitory activity (EC50: 48 microM) against HSV-2 and a modest inhibitory activity (EC50: 110 microM) against HIV-1, respectively.