Phytochemical and synthetic studies on bioactive secondary metabolites from Apiaceae plants growing in Mediterranean and Middle-East regions

Natural products represent a remarkable source of lead molecules for drug discovery, given their impressive structural diversity and their still unexplored potential. Considering that more than 90% of the world’s biodiversity still waits to be investigated, Nature continues to be a gold mine of new chemotypes and pharmacophores. Thus, taking into account all the potential sources, including plants, fungi, bacteria, and marine environment, approximately one-third of all New Molecular Entities (NMEs) approved by Food and Drug Administration (FDA) derives from natural products. In this context, the research work reported in this Ph.D. thesis has been focused on the phytochemical investigation of plants belonging to the Iranian and Northern African flora, in order to discover and rationalize their pharmacological potential. In particular, the first part of my work has been devoted to the characterization of the polyacetylene fraction of Echinophora platyloba, which pointed out a new interesting TRPA1 modulating activity of C14 polyacetylenes isolated from this Iranian endemic plant. Subsequently, the bio-guided fractionation of the apolar extract obtained from Daucus virgatus, a Tunisian endemic plant, led to the isolation of angeloylated germacranolides showing a promising Plasmodium transmission blocking activity. Moreover, the complete phytochemical characterization of D. virgatus apolar extract has resulted in the isolation of additional antiproliferative secondary metabolites. Part of my Ph.D. project has been spent at University College of Dublin (UCD), to design and initiate a synthetic strategy for the preparation of daucovirgolide G, the angeloylated germacranolide that showed the most promising anti-malarial activity, among all those isolated from D. virgatus. The total synthesis of daucovirgolide G, which is still in progress, will have as final goal the preparation of the active compound and of several analogues to be pharmacologically evaluated. The results obtained during my Ph.D. have been reported in nine papers already published or ready for publication

Paestum dietary habits during the Imperial period: archaeological records and stable isotope measurement

In historical contexts, analyses of carbon and nitrogen stable isotopes can be useful to answer different question on dietary behavior and to crosscheck information, drawn from texts and classical archaeological investigations. In this study the Isotope Ratio Mass Spectrometry (IRMS) facility installed at the IRMS-SUN Laboratory of the Second University of Naples is presented. Moreover, results coming from application of stable isotope analyses to bone collagen extracted from human remains of the necropolis of "Porta Sirena" in Paestum will be discussed. Finally, a combined analyses of archaeological and historical record and stable isotope measurements permits to expand our knowledge on diet in Roman Paestum.</p

delta C-13 signatures of organic aerosols:Measurement method evaluation and application in a source study

Analysis of the stable carbon isotope 13C in organic carbon (OC) can give insight into sources and atmospheric processing of carbonaceous aerosols, provided the 13C source signatures are known. However, only few data on 13C signatures of OC emitted by common sources of carbonaceous aerosol are available in Europe. We present and evaluate an improved version of a measurement method to obtain δ13C signatures on organic aerosols desorbed from filter samples at three different desorption temperatures (200 °C, 350 °C and 650 °C) and apply it in a source study. With our calibration approach, the reproducibility of a L-Valine reference material desorbed at a single temperature step of 650 °C shows a standard deviation of 0.19‰ over a period of more than one year. The average δ13C value for this reference material over 248 measurements is −24.10‰, which shows only a slight bias to the nominal value of −24.03‰. Repeated analysis of ambient filter samples desorbed at three temperature steps show typical standard deviations of about 0.3‰ for all temperature steps (200 °C, 350 °C and 650 °C). Isotopic fractionation due to partial thermal desorption during the individual temperature steps was tested on single compound reference materials. It showed significant isotopic fractionation only at temperature steps, in which a very minor fraction of the compound was desorbed. Possible isotope effects caused by charring of organic material were investigated and found to be not significant. The thermal desorption method was applied to various source filter samples from the region of Naples, Italy. We analyzed two different biomass burning sources, exhaust from a city bus and traffic emissions collected in a tunnel and compared these to ambient filter samples from the same region. δ13C signatures of the total OC show values in a narrow range of about −28‰ to −26‰ for all sources, which does not allow a source apportionment only based on 13C. Nevertheless, the results add information to a source inventory of δ13C, where information of 13C in organic aerosol from specific emission sources are rare. City bus emissions show little variation of δ13C over the temperature steps, whereas biomass burning aerosol is enriched in 13C for OC desorbed at 650 °C. For PM10 samples in the urban tunnel an enrichment in δ13C at the 650 °C temperature steps was observed, which is likely caused by the contribution of carbonate carbon to the carbonaceous material desorbed at this temperature step

The potential of natural products for targeting PPAR α

Peroxisome Proliferator Activated Receptors (PPARs) α, -γ and -β/δ are ligand-activated transcription factors and members of the nuclear hormone receptor superfamily. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, e. g. rosiglitazone and pioglitazone) are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPARγ, while PPARα is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating PPARα with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this "hot" target

N2O influence on isotopic measurements of atmospheric CO2

In spite of extensive efforts, even the most experienced laboratories dealing with isotopic measurements of atmospheric CO2 still suffer from poor inter-laboratory consistency. One of the complicating factors of these isotope measurements is the presence of N2O, giving rise to mass overlap in the isotope ratio mass spectrometer (IRMS). The aim of the experiment reported here has been twofold: first, the re-establishment of the correction for ‘mechanical’ interference of N2O in the IRMS, along with its variability and drift, and the best way to quantitatively determine the correction factors. Second, an investigation into secondary effects, i.e. the influence of N2O admitted with the CO2 sample on the ‘‘cross contamination’’ between sample and (pure CO2) working gas. To make the suspected effects better detectable, isotopically enriched CO2 gas with different concentrations of N2O has been measured for the first time. No evidence of secondary effects was observed, from which we conclude that N2O is not a major player in the inter-laboratory consistency problems. Still, we also found that the determination of the ‘mechanical’ N2O correction needs to be very carefully determined for each individual IRMS, and should be periodically re-determined. We show that the determination of the correction should be performed using CO2/N2O mixtures with concentration ratios around that of the atmosphere, as the extrapolation from pure gas end member behaviour will give erroneous results due to non-linearities. For our IRMS, a VG SIRA series II, we find a correction of 0.23‰ for δ45CO2 and 0.30‰ for δ46CO2 of atmospheric samples, (with 0.85‰ mixing ratio). This implies that the relative ionisation efficiency (E) value associated with this machine is 0.75.

Dalla cava all’epigrafe. Primi risultati di una ricerca multidisciplinare sulle iscrizioni dalla necropoli tardoantica di Abellinum-Atripalda (AV).

Il contributo presenta i primi risultati delle analisi isotopiche condotte su un campione selezionato di epigrafi tardoantiche, datate 'ad annum', dalla basilica di Abellinum-Atripalda (AV). Lo studio riguarda le caratterizzazioni e le provenienze dei marmi di supporto, con le prime considerazioni storiche che derivano dall'interpretazione congiunta dei dati provenienti dal terreno e dalle analisi scientifiche

The effects of prescribed burning on Pinus halepensis Mill. as revealed by dendrochronological and isotopic analyses

International audiencePrescribed burning is used in several countries to manage Mediterranean ecosystems mainly to reducethe risk of high-intensity wildfires. As the physiological response of overstory trees to prescribed burninghas received scant attention in the scientific literature, the main objective of this study was to determinewhether prescribed burning impacts the growth and ecophysiological responses of stands of the Aleppopine (Pinus halepensisMill.). Basal area, carbon, oxygen, and nitrogen isotopic compositions were ana-lyzed before and after the burning event at an experimental site and at a nearby unburned area usedas control, both in the co-existing old dominantP. halepensistrees and in the youngest individuals.Our results suggest that the oldest pines experienced more favorable growing conditions after prescribedburning probably through higher water and nutrient availability, at least in the short term. The youngestindividuals mostly likely suffered from an increase in competition with the older co-existing trees. Thesedifferences in physiology suggest the need to understand and evaluate, in the prescribed burning man-agement plans, the growth and survival of burned trees of different ages in order to maximize the positiveeffects and reduce possible negative impacts

14C AMS measurements in tree rings to estimate local fossil CO2 in Bosco Fontana forest (Mantova, Italy)

International audienceRadiocarbon concentration in atmosphere changes overtime due to anthropogenic and natural factors. Species growth preserves the local atmospheric radiocarbon signature over their life span in the annual tree rings and make it possible to use tree rings for the monitoring of changes in fossil-fuel emissions due to an increase of traffic exhaust, during the last decades.In this paper, the CIRCE AMS system has been used to measure the 14C concentration in tree rings of plants grown near an industrial area and a very busy State Road, in a forest in north Italy. Preliminary results related to tree rings of several years of plants respectively near and far the emitting sources are displayed, in order to estimate the local pollution effect. It is possible to find a dilution in years 2000 and 2006 in both the trees analysed, but not enough data have been analysed yet in order to distinguish the fossil dilution derived from the street vehicular traffic or that from the industries