A comparative photochemical study on the behavior of 3,3'-dihydroxyflavone and its complex with La(III) as generators and quenchers of reactive oxygen species.

A 1:1 complex between 3,3'-dihydroxyflavone (DHF) and La(III) (DHF-La(III)) is formed in methanolic solution with the relatively high apparent stability constant value of 2.3×10(6) and a calculated standard entropy change of 88.2 J mol(-1) K(-1), both at 25 °C. The photophysical properties of the complex and the free flavonoid are discussed in comparison to the well known related compound 3-hydroxyflavone. The ligand photogenerates O2((1)Δg) by energy transfer from its excited triplet state ((3)DHF(*)) to dissolved ground state oxygen, with a quantum yield of 0.13. (3)DHF(*) is quenched by La(III) with a rate constant close to the diffusion-controlled value. The respective abilities of the free flavonoid and DHF-La(III) as quenchers of the riboflavin-photogenerated reactive oxygen species singlet molecular oxygen (O2((1)Δg)) and superoxide radical anion (O2(-)) have been investigated. Both individual compounds were photoirradiated with visible light in the presence of the flavin as the only light-absorbing compound. A detailed kinetics and mechanistic study employing polarographic monitoring of oxygen uptake and time resolved detection of O2((1)Δg) phosphorescence indicates that DHF and the complex react with O2((1)Δg) and O2(-) by a non simple mechanism. The former deactivates O2((1)Δg) in a predominant physical fashion, a fact that constitutes a desirable property for antioxidants. It was found that metal chelation greatly enhances the ability of DHF as an overall O2((1)Δg) quencher.

Interaction between 2',4-dihydroxychalcone and the N, f, e conformers of bovine serum albumin: influence of temperature and ionic strength.

UV-Vis spectroscopy was used to study the interaction between the 2',4- dihydroxychalcone, flavonoid which is known to have anti-tumor activity in vitro, and others biological properties, and the N, F and E conformers of bovine serum albumin at different ionic strengths and temperatures. The Klotz model was found to be adequate to determine the constants and number of binding sites. The reaction was found to be exothermic and spontaneous. The number of binding sites decreases and the reaction is more exergonic along with the increase in ionic strength and the conformational change of N to E. The reactions were necessarily hydrophobic and followed by a process of ionic character.

Effects of dimethylformamide and L-menthol permeation enhancers on transdermal delivery of quercetin.

In this work a feasibility study of transdermal delivery system for quercertin (Q) in carbopol gel through abdominal hairless pig skin in vitro was performed. Dimethylformamide (DMF) and L-menthol (M) were selected as enhancers. Permeation experiences were carried out by using Franz-type diffusion cells. Phosphate saline buffer (pH 7.4) was used in the receptor compartments. All the system was maintained at 32 +/- 0.5 degrees C with a circulating water jacket and magnetic stirring (180 rpm). Samples were analysed by UV-VIS spectrophotometer at 255 nm. Flux (Jm) values, permeation (P) and diffusion (D) coefficients were obtained. Results of Q in CG permeation experiences with different percentages of DMF and M showed that 16.7% DMF and 1.95% L-menthol enhancers were the best quantities for the system tested. Enhancer effect can be attributed to direct action on membrane structure by promoting its distension. Therefore, enhancer substitutes for water in pores, improving active principal permeation through pig skin. M significantly increases Q permeation about 17 times higher than control. The results of permeation experiments with M and DMF using the same enhancer concentration (1.42%) conclude that M action is 9 times higher than DMF, approximately, indicating that M is an effective enhancer for a transdermal therapeutic system of Q in CG as vehicle.

Salicylic acid permeation: a comparative study with different vehicles and membranes.

Considering the skin's function, different dermal pharmaceutical forms can be developed according to the type of therapeutic activity, active principle and excipients involved in the formulation, such as "transdermal preparations". In the present study, the permeation parameters of the non-steroidal anti-inflammatory drug, salicylic acid (SA) through synthetic membrane, polyvinyliden difluoride, and a biological membrane, egg shell membrane, with different vehicles, propylene glycol, isopropyl alcohol and carbopol gel, were determined. The reported physicochemical parameters of SA from CG were significantly higher than those obtained using PG and IP. This is attributed to the lipophilic nature of the vehicle that facilitates the release and penetration of the active principle, thus acting sinergically. The permeation profiles of SA allow us to state that permeation kinetics is of first order, so that the flux values obtained are in direct proportion to the specific rates of drug release.

Synergism of flavonoids with bacteriostatic action against Staphylococcus aureus ATCC 25 923 and Escherichia coli ATCC 25 922.

In our previous studies, bacteriostatic action of flavonoids against Staphylococcus aureus ATCC 25 923 and Escherichia coli ATCC 25 922 was demostrated. In the present work synergism of their combinations in order to improve the bacteriostatic action against the same microorganisms was determined. The experiences were made in nutritive broth, maintaining constant one drug concentration (20 microg/ml) and increasing the other one. A turbidimetric kinetic method was used and by means of a mechanism previously proposed, the minimal inhibitory concentrations (MIC's) of each flavonoid combination were determined. The MIC's for assayed combinations against S. aureus were: variable morin - constant rutin: 157.44 microg/ml and variable quercetin - constant morin: 29.9 microg/ml. The values obtained against E. coli were: variable morin - constant rutin: 78.5 microg/ml; variable quercetin - constant rutin: 47.4 microg/ml; variable quercetin - constant morin: 25 microg/ml; variable morin - constant quercetin: 27.4 microg/ml.

Bacteriostatic action of synthetic polyhydroxylated chalcones against Escherichia coli.

In previous work the bacteriostatic action of trihydroxylated chalcones against Staphylococcus aureus ATCC 25 923 was investigated. In this work the action of 2',4',2-(OH)3-chalcone, 2',4',3-(OH)3-chalcone and 2',4',4-(OH)3-chalcone against Escherichia coli ATCC 25 922 was evaluated. Growth kinetic curves of E. coli were made in nutritive broth added with increasing drug concentrations. The specific growth rates of the microorganisms were calculated by a kinetic turbidimetric method, which was previously probed and the minimal inhibitory concentrations (MIC's) were evaluated by a mechanism of action proposed. The MICs of 2',4',3-(OH)3-chalcone and 2',4',2-(OH)3-chalcone were 46 microg/ml and 122 microg/ml, respectively. The 2',4',4-(OH)3-chalcone was inactive. The MIC value of 2',4',3-(OH)3-chalcone (46 microg/ml), more active than 2',3-(OH)2-chalcone (72.2 microg/ml) may be due to the introduction of an electron donating group (-OH) at position 4' in the aromatic A-ring, which activates the region that includes the 2'-hydroxyl neighbor group and the alpha,beta-unsaturated carbonyl group.

Bacteriostatic action of synthetic polyhydroxylated chalcones against Escherichia coli.

In previous work the bacteriostatic action of trihydroxylated chalcones against Staphylococcus aureus ATCC 25 923 was investigated. In this work the action of 2,4,2-(OH)3-chalcone, 2,4,3-(OH)3-chalcone and 2,4,4-(OH)3-chalcone against Escherichia coli ATCC 25 922 was evaluated. Growth kinetic curves of E. coli were made in nutritive broth added with increasing drug concentrations. The specific growth rates of the microorganisms were calculated by a kinetic turbidimetric method, which was previously probed and the minimal inhibitory concentrations (MICs) were evaluated by a mechanism of action proposed. The MICs of 2,4,3-(OH)3-chalcone and 2,4,2-(OH)3-chalcone were 46 microg/ml and 122 microg/ml, respectively. The 2,4,4-(OH)3-chalcone was inactive. The MIC value of 2,4,3-(OH)3-chalcone (46 microg/ml), more active than 2,3-(OH)2-chalcone (72.2 microg/ml) may be due to the introduction of an electron donating group (-OH) at position 4 in the aromatic A-ring, which activates the region that includes the 2-hydroxyl neighbor group and the alpha,beta-unsaturated carbonyl group.

A comparative study of bacteriostatic activity of synthetic hydroxylated flavonoids

Among other properties, flavonoids present a notable bacteriostatic activity. In this paper, minimal inhibitory concentrations (MICs) of 5,7,4'-trihydroxyflavanone (naringenin), 5,7-dihydroxyflavone and 2',4',4- trihydroxychalcone (isoliquitirigenin) against Staphylococcus aureus ATCC 25 923 were determined and compared to values obtained for other chalcones and flavanones previously investigated. Specific growth rates and MICs were determined by a turbidimetric kinetic method. The observed sequence MICflavanone (inactive) >MIC7-hidroxyflavanone (197.6 µgml-1)>MIC5,7,4'-trihydroxyflavanone (120 µgml-1) showed that the introduction of an electron donating group (-OH) causes an increase in bioactivity. On the other hand, the comparisons MIC5,7,4'-trihydroxyflavanone (120 µgml-1) >>> MIC2',4',4-trihydroxychalcone (29 µgml-1) and MIC5,7-dihydroxyflavone (105 µgml-1) >>> MIC2',4'-dihydroxychalcone (28.8 µgml-1) indicated that the chalcone structure is the most favourable for bacteriostatic activity within the flavonoid family.

Structure-biological activity relationship of synthetic trihydroxilated chalcones

The bacteriostatic activity of 2',4',2'-trihydroxychalcone; 2',4',3'-trihydroxychalcone and 2',4',4'-trihydroxychalcone, prepared by condensation of 2,4-dihydroxyacetophenone and benzaldehyde substituted, against "Staphylococcus aureus" ATCC 25923 was assayed by agar plate method. The three compounds presented important inhibition halos. In order to elucidate structure-activity relationships, the minimal inhibitory concentrations against "S. aureus"were determined by the broth dilution method and the results obtained were compared to that of 2',4'-(OH)2>MIC 2',4',4'-(OH)3>>MIC 2',4',2-(OH)3. these results showed that the introduction of an electron donating group (-OH) in the aromatic B-ring causes an increase in bioactivity, and that the intensity of action depends on the position of the OH substitute.