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Materia medica e prodotti naturali nella Chimica Farmaceutica
Get PDFViene considerato che la valutazione dei farmaci e delle diete descritte in testi
antichi, così come quelle utilizzate da popoli indigeni con metodi moderni biomedici
e target biochimici potrebbe essere un approccio promettente per la scoperta di
nuovi farmaci e agenti biochimici.
Partendo da questa ipotesi di lavoro in questi anni di dottorato si è investigato sulla
De Materia Medica di Dioscoride e sulla etnofarmacopea dei Popoluca, discendenti
degli Olmechi, ubicati nello stato messicano di Veracruz.
In uno screening preliminare, base di questo progetto, l’estratto della Seseli praecox
ha mostrato interazione con il recettore cannabinoide (CB) in vitro. Il genere Seseli è
stato citato varie volte nella traduzione della De Materia Medica di Matthioli (1568),
indicandola per il trattamento della disuria, nel respiro affannoso e contro la tosse
cronica.
L’isolamento dei metaboliti secondari è stato effettuato mediante tecniche
cromatografiche quali VLC, CC, HPLC, SPE mentre la delucidazione dei composti
isolati è stata determinata attraverso lo studio degli spettri NMR mono (1H, 13C) e
bidimensionali (ROESY, COSY, HMBC, HSQC), di massa esatta Q-TOF HRMS e
attraverso la spettroscopia UV.
Lo studio fitochimico della S. praecox (appartenente alla famiglia delle Apiaceae)
una specie endemica sarda, ha portato all’ottenimento di un nuovo cromone e di un
nuovo poliacetilene. Il 5-hydroxy-6-(2-Z-butenyl-3-hydroxymethyl)-7-methoxy-2-
methylchromone, ha dimostrato possedere interessanti proprietà citotossiche verso le
linee tumorali Jurkat T e HL60. Il nuovo poliacetilene è stato delucidato come
l’heptadeca-1-ene-4,6-diyne-3,10-diol (dihydroseselidio). Inoltre abbiamo isolato
composti già noti come furocumarine lineari (psoralene, phellopterina, imperatorina,
bergaptene, marmesina) e i poliacetileni falcarinolo e falcarindiolo. Abbiamo trovato
che il falcarinolo, conosciuto per le sue proprietà allergeniche, citotossiche,
antifunginee e antibatteriche, mostra attività di binding recettoriale verso i recettori
CB1 in vitro (come antagonista), mentre in vivo aggrava la formazione di edema
nella pelle indotta dall’istamina.
Per meglio capire il ruolo proallergenico del falcarinolo abbiamo studiato anche i
prodotti di degradazione (4,5-dihydrofalcarinolo (ginsenoyne J), falcarinone e l’Eheptadeca-
1,8-diene-4,6-diyne-3,10-diolo). Concludiamo che il falcarinolo agisce
come proallergenico nella pelle attraverso una sua azione antagonistica verso i recettori CB1 impedendo che l’anandamide eserciti la sua costitutiva proprietà
antinfiammatoria.
In un secondo lavoro, che riguarda la farmacopea dei Popoluca, la nostra attenzione
si è rivolta ad una specie che, in uno studio preliminare, aveva mostrato attività
antivirale in vitro: la Securidaca diversifolia (appartenente alla famiglia delle
Polygalaceae). Infatti i Popoluca utilizzano il macerato della corteccia radicale per
curare le malattie febbrili, incluso il morbillo e in misura minore, la diarrea.
Da questa specie abbiamo isolato tre nuovi benzofenoni (2,4-dihydroxy-3-methoxybenzophenone,
2,4-dihydroxy-3,3’-dimethoxy-benzophenone, benzophenone 3’,4’-
methylendioxy-2,4-dihydroxy-3-methoxy-benzophenone). I primi 2 hanno mostrato
di possedere una moderata attività di inibizione verso l’ Herpes simplex virus di tipo
1, in vitro. Sono stati inoltre isolati i composti noti benzyl 2-hydroxy-6-
methoxybenzoate, benzyl 2,6-dimethoxybenzoate e l’isovanillina.
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It has been suggested, that the evaluation of drugs and diets described in ancient
texts as well as those used by indigenous populations with modern biomedical
methods and targets could be a promising approach for the discovery of new drugs
and biochemical tools. Following this working hypothesis in this PhD thesis we
focused on Dioscorides’ De Materia Medica as well as on the ethnopharmacopoeia
of the Popoluca, who are descendents of the Olmecs and live in the state of
Veracrruz (Mexico). In a preliminary screening at the beginning of this project the
extract of Seseli praecox has shown interactions with the cannabinoid (CB) receptor
in vitro. The genus Seseli is cited various times in Matthioli’s translation of the De
Materia Medica (1568) where the indication against dysuria, respiration problems
and chronic cough are mentioned. The isolation of the secondary metabolites was
conducted with the help of chromatographic techniques such as VLC, CC, HPLC,
SPE, while the structure delucidation of the pure compounds was achieved by the
studying of mono- (1H, 13C) and bidimensional (ROESY, COSY, HMBC, HSQC)
NMR spectra as well as with the help of Q-TOF HRMS and UV spectroscopy. The
phytochemical study of S. praecox (Apiaceae), an endemic species from Sardinia,
led to the isolation and characterization of one new chromone and one new
polyacteylene. 5-hydroxy-6-(2-Z-butenyl-3-hydroxymethyl)-7-methoxy-2-
methylchromone showed interesting cytotoxic properties against Jukat T and HL60
cancer cell lines. The new polyacetylene was identified as heptadeca-1-ene-4,6-
diyne-3,10-diol (dihydroseselidio). Moreover, previously isolated compounds like
linear furocoumarins (psoralene, phellopterina, imperatorina, bergaptene,
marmesina) and polyacetylenes such as falcarinol and falcarindiol were obtained.
We found that falcarinol, well-known for its allergenic, cytotoxic, antifungal as well
as antibacterial properties showed antagonistic CB1 receptor binding affinity in vitro,
while it aggravates histamine induced oedema formation in skin. In order to better
understand the proallergenic role of falcarinol we also studied its degradation
products (4,5-dihydrofalcarinolo (ginsenoyne J), falcarinone e l’E-heptadeca-1,8-
diene-4,6-diyne-3,10-diolo). We conclude that falcarinol acts as a proallergenic
agent in skin via its antagonitsic affinity towards CB1 receptors thereby preventing
the constitutive antiinflammatory action of anandamide.
In a second study focussing on the farmacopoeia of the Popoluca our attention fell
upon a species showing antiviral activity in vitro: Securidaca diversifolia
(Polygalaceae). The Popoluca use in fact a maceration of the root bark for the treatment of fevers, including measles and to a minor extent also against diarrhoea.
From this species we obtained three new benzophenones (2,4-dihydroxy-3-methoxybenzophenone,
2,4-dihydroxy-3,3’-dimethoxy-benzophenone, benzophenone 3’,4’-
methylendioxy-2,4-dihydroxy-3-methoxy-benzophenone). The first two showed
moderate inhibitiory activity against Herpes simplex virus type 1 in vitro. Moreover,
previously isolated compounds such as benzyl 2-hydroxy-6-methoxybenzoate,
benzyl 2,6-dimethoxybenzoate and isovanilline were obtained
Protein secondary structure prediction: novel methods and software architectures
Get PDFOwing to the strict relationship between protein structure and function, the
prediction of protein tertiary structure has become one of the most important
tasks in recent years. Despite recent advances, building the complete
protein tertiary structure is still not a tractable task in most cases; in the
absence of a clear homology relationship the problem is often decomposed
into smaller sub tasks, including the prediction of the secondary structure.
Notwithstanding the large variety of dierent strategies proposed over the
years, secondary structure prediction is still an open problem, and few advances
in the field have been made in recent times.
In this thesis, the problem of secondary structure prediction is firstly analyzed,
identifying five different information sources related to the biological
essence of the problem, in order be exploited in a learning system. After
describing a general software architecture and framework aimed at dealing
with the issues related to the engineering and set up of prediction systems
applied to real-world problems, dierent techniques based on the encoding
and decoding of biological information, together with custom software
architectures, are presented.
The different proposals are assessed experimentally. The best improvements
are consistent with the recent advances in the field (about 1-2% in the last
ten years), conforming the validity of the assumption that the correlation
sources identified can be further exploited to improve predictions
Application of artificial neural networks in hydrogeology: identification of unknown pollution sources in contaminated acquifers
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Utilizzo di tecniche elettrofisiologiche e comportamentali indirizzate al controllo eco-compatibile di popolazioni di insetti di interesse ambientale, sanitario e agronomico
Get PDFThe Mediterranean fruit fly, Ceratitis capitata Wied., is a worldwide pest for horticulture because of its high biological potential, the difficulty of control and the broad polyphagy, mainly addressed, in Southern Europe, to pomaceous (apples and pears) and citrus (oranges) cultures. Information in the literature on the olfactory sensitivity in the medfly is still incomplete and only a few data are reported on the responses to alcohols, aldehydes, esters and acids, but with no reference to the physiological state (Light et al., 1988).
Aim of the present work was to obtain further knowledge on the typology and topology of olfactory chemosensilla on both - medial and lateral - antennal surfaces in males and females. In addition, their electrophysiological activity has been evaluated in response to extracts of fruits and foliage from various host-plants and their primary compounds in two different -wild and lab reared- medfly populations, also in relation to the sex and to the physiological (virgin vs. mated) state of the insects.
HRSEM morphological analysis has highlighted the presence of 4 different olfactory chemosillum types on both the medial and lateral antennal surface which may be classified as basiconic, clavate, trichoid and grooved sensilla. No difference in number and distribution has been observed between sexes, except for the female lateral surface, where a statistically higher number of clavate sensilla was detected.
The EAG responses show that 1) the male olfactory sensitivity of lab reared medflies to headspace collected from fruits of lemon, orange, clementine, prickly pear, apple and their relative foliage was higher than that of females, while an opposite situation was found for wild insects; 2) same results were obtained when virgin and mated insects were considered; 3) virgin males and females displayed a higher sensitivity than the mated ones in the wild and lab populations, respectively; 4) within each population, the olfactory sensitivity was higher in mated males than mated females in lab population, while the opposite was found for wild insects.
The olfactory sensitivity of the medfly to host-plant fruits and foliage in relation to physiological state and rearing conditions is discussed
Design, synthesis and characterisation of homoleptic and heteroleptic 1,2-dichalcogenolene platinum and gold complexes with potential ICT applications: an experimental and theoretical study
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Applications of perturbation theory in black hole physics
Get PDFBlack holes have many faces. Arguably, they are the most interesting objects in theoretical physics, revealing the elusive connection between gravity and quantum mechanics. Within the gauge/string duality they provide useful insights on strongly coupled quantum field theories
and on quantum gravity. Furthermore, probing the strong curvature regime of any gravity theory, black holes carry the imprint of possible strong curvature corrections to General Relativity. Finally, beside their unique theoretical properties, several experimental evidences
suggest that astrophysical black holes exist in nature and they are believed to be very common objects in the universe. In this dissertation we discuss several applications of linear perturbation theory in black hole physics. As applications in theoretical physics, we study
perturbations of dilatonic black holes in Einstein-Maxwell theory and the holographic properties of the dual field theory via the Anti de Sitter/Condensed Matter duality. Furthermore we discuss a method to compute long-lived quasinormal modes of Schwarzschild-Anti de Sitter
black holes and we study vortex black hole solutions in three dimensional Anti de Sitter gravity. As applications in astrophysics, we discuss how the characteristic oscillations of black holes in string-inspired theories of gravity can provide observable signatures of deviations from
General Relativity. We study two well-motivated effective theories: Dynamical Chern-Simons gravity and Einstein-Dilatonic-Gauss-Bonnet gravity. We conclude by discussing the black hole paradigm. Motivated by the lacking of a definitive answer on the existence of astrophysical
black holes, we study some viable alternatives, generally called “black hole mimickers”. We focus on two representative cases: static thin-shell gravastars and superspinars. We discuss their stability, gravitational-wave signature and viability as astrophysical objects
