RESUMEN
The synthesis, in vitro evaluation and conformational study of penetratin and structurally related derivatives acting as antibacterial agents are reported. Among the compounds evaluated here, two methionine sulphoxide derivatives (RQIKIWFQNRRM[O]KWKK-NH2 and RQIKIFFQNRRM[O]KFKK-NH2 ) exhibited the strongest antibacterial effect in this series. In order to better understand the antimicrobial activity obtained for these peptides, we performed an exhaustive conformational analysis using different approaches. Molecular dynamics simulations were performed using two different media (water and trifluoroethanol/water). The results of these theoretical calculations were corroborated using experimental CD measurements. The electronic study for these peptides was carried out using molecular electrostatic potentials obtained from RHF/6-31G(d) calculations. In addition, the non-apeptide RQIRRWWQR-NH2 showed strong inhibitory action against the Gram-negative and Gram-positive bacteria tested in this study.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Proteínas Portadoras/química , Proteínas Portadoras/farmacología , Secuencia de Aminoácidos , Infecciones Bacterianas/tratamiento farmacológico , Péptidos de Penetración Celular , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Conformación ProteicaRESUMEN
The synthesis, in vitro evaluation and conformational study of KKWKMRRNQFWIKIQR-NH(2), HFRWRQIKIWFQNRRMKWKK-NH(2) and RQPKIWFPNRRKPWKK-NH(2) acting as antifungal agents are reported. These peptides displayed a moderate but significant antifungal effect against both pathogenic fungi Candida albicans and Cryptococcus neoformans. The conformational analysis of these peptides was carried out using both theoretical and experimental methods.
Asunto(s)
Antifúngicos/síntesis química , Péptidos/síntesis química , Secuencia de Aminoácidos , Antifúngicos/química , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Dicroismo Circular , Cryptococcus neoformans/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Péptidos/química , Péptidos/farmacología , Estructura Secundaria de ProteínaRESUMEN
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.
Asunto(s)
Adyuvantes Farmacéuticos/farmacología , Dimetilformamida/farmacología , Mentol/farmacología , Quercetina/farmacocinética , Absorción Cutánea/efectos de los fármacos , Resinas Acrílicas , Administración Cutánea , Algoritmos , Animales , Antioxidantes/administración & dosificación , Antioxidantes/farmacocinética , Difusión , Sistemas de Liberación de Medicamentos/métodos , Estructura Molecular , Permeabilidad/efectos de los fármacos , Polivinilos/química , Quercetina/administración & dosificación , Piel/efectos de los fármacos , Piel/metabolismo , PorcinosRESUMEN
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.
Asunto(s)
2-Propanol , Membrana Celular/metabolismo , Cáscara de Huevo/metabolismo , Propilenglicol , Ácido Salicílico/administración & dosificación , Ácido Salicílico/farmacocinética , 2-Propanol/administración & dosificación , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/metabolismo , Antiinflamatorios no Esteroideos/farmacocinética , Permeabilidad , Propilenglicol/administración & dosificación , Ácido Salicílico/metabolismoRESUMEN
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.