The essential oils of Thymus vulgaris L., of Eavandula R.C. hybrid and Mentha piperita L. were tested in vitro against the pathogenic fungi Rhizoctonia solani Kuhn, Pythium ultimum Trow var. ultimum, Eusarium solani (Mart.) Sacc, Colletotrichum tindemuthianum (Sacc. & Magn.) Briosi & Cav.Ali the oils tested inhibited fungal growth. The most effective oil was that of thyme, with a fungicidal activity attributable to thymol, found in a concentration of 50.06% in the oil tested. SEM observations revealed that these oils cause degeneration of the fungal hyphae which appeared emptied of their cytoplasmic content.
In view of the pharmacological interest in phenolic substances, we have determined the total amount of anthocyanins and polyphenols present in the berries of several cultivars of Ribes, Rubus, and Vaccinium genera. The in vitro antiradical activity of the crude extracts on chemically-generated superoxide radicals as well as the inhibitory activity towards the enzyme xanthine oxidase were studied. All the crude extracts examined showed a remarkably high activity towards chemically-generated superoxide radicals. The activities were greater than those expected on the basis of the quantities of anthocyanins and polyphenols present in the samples. Furthermore, the extracts showed a certain inhibitory activity towards xanthine oxidase. Ribes nigrum extracts exhibit the highest activity, being the richest in both anthocyanins and polyphenols. On the other hand, Ribes rubrum extracts seem to contain more active substances than the other crude extracts.
Starting from the inhibitory activity of the flavonoid Quercetin, a series of 4H-1-benzopyran-4-one derivatives was synthesized and tested for inhibition of aldose reductase, an enzyme involved in the appearance of diabetic complications. Some of the compounds obtained display inhibitory activity similar to that of Sorbinil but are more selective than Quercetin and Sorbinil with respect to the closely related enzyme, aldehyde reductase, and also possess antioxidant activity. Remarkably, these compounds possess higher pKa values than carboxylic acids, a characteristic which could make the pharmacokinetics of these compounds very interesting. Molecular modeling investigations on the structures of inhibitors bound at the active site of aldose reductase were performed in order to suggest how these new inhibitors might bind to the enzyme and also to interpret structure-activity relationships.
Genotoxic properties of essential oils from Anthemis nobilis L., Artemisia dracunculus L., Salvia officinalis L., Salvia sclarea L., Satureja hortensis L., Satureja montana L., Thymus capitatus L., Thymus citriodorus Schreb., Thymus vulgaris L., Citrus bergamia Risso, were studied with Bacillus subtilis rec-assay and Salmonella/microsome reversion assay. The essential oil of Artemisia dracunculus L. "Piemontese" turned out to be active in the rec-assay but not in the Salmonella test. DNA-damaging activity was demonstrated to be due to the estragol component of the oil. Advantages of the combined use of these two short-term microbial assays in genotoxic studies are discussed.
A model of the interaction of substrates and inhibitors with
xanthine oxidase (XO) based on similarity
concepts and molecular modeling is introduced and discussed, and
previous literature is reexamined in the light of
recent insights into the mechanism and structure of XO. Use is
made of quantum-chemical calculations with the
inclusion of solvent effects, molecular superimposition with
least-squares fitting algorithms, and molecular
electrostatic
potentials. First, the relative stabilities of the tautomeric
forms of the physiological substrates, xanthine and
hypoxanthine, are calculated both in vacuo and in water in
order to select the most abundant form(s) at
physiological
pH: the two substrates prove to be stable in their lactam forms, with
a dominance of the N7-H tautomer for xanthine
and of N9-H for hypoxanthine. The structures of
xanthine and hypoxanthine are then superimposed, and their
relative
orientation with respect to the molybdenum center of XO is suggested.
The criteria used for superimposition reflect
the importance of functional groups of xanthine and hypoxanthine, as
inferred from experimental work. In particular,
the carbonyl oxygen common to the two substrates is given special
consideration on account of its determinant role.
The results show that the most important functional groups of the
two substrates can be successfully superimposed
by means of a rotation that exchanges the five-membered with the
six-membered rings of xanthine and hypoxanthine
with respect to molybdenum. The close similarity of the
electrostatic potentials of the two superimposed molecules
adds weight to the proposed orientation of the substrates in the
binding site. The model of interaction is then tested
and further developed using a series of previously-synthesized
dimensional analogs of xanthine and hypoxanthine.
The results confirm that the correct positioning of the carbonyl
group is essential if a productive interaction with XO
is to be achieved and allow us to map the dimensions of the active site
starting from the superimposition of the
physiological substrates. Two hypotheses regarding the amino acid
residues interacting with the important carbonyl
oxygen of the substrates are then put forward on the basis of
spectroscopic and biochemical evidence: they are
postulated to be one lysine or one protonated glutamic acid residue.
In an attempt to unify the binding of substrates
and inhibitors, the model is extended to the inhibitors of XO by
superimposing the most interesting inhibitors developed
by Robins on xanthine and hypoxanthine. This allows us to define
the most suitable location of the phenyl rings of
these inhibitors with respect to the superimposition of the substrates.
Intriguingly, the superimpositions of the most
active inhibitors are consistent with a unique location of their phenyl
rings, even though they are in different positions
on the purine ring. Finally, the flavone, which is a potent
inhibitor of XO and is currently under investigation by
the authors, is accounted for by these findings and succe...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.