IIBYT   23944
INSTITUTO DE INVESTIGACIONES BIOLOGICAS Y TECNOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Membrane interaction of Dihydropyrimidines
Autor/es:
SANCHEZ BORZONE, M; MARIANI, ME; VENUGOPALA, K; BARTHI, O; GLEISER RM,; GARCIA, DA
Lugar:
Santiago del estero
Reunión:
Congreso; XLIV Reunion Anual de la Sociedad Argentina de Biofisica (SAB); 2015
Institución organizadora:
Sociedad Argentina de Biofisica (SAB)
Resumen:
Dihydropyrimidines (DHPMs) derivatives have a signficant role in medicinal chemistry for various pharmacologicalactivities, such as anticancer, antibacterial, antifungal,antihypertensive, antitubercular, antimalarial, antiviral, and anti-inflammatory activities. The high hydrophobicity of DHPMs permits to supposethat many of these effects could involve their interaction with biologicalmembranes. The purpose of the present study was to determine the ability of twoDHPM analogs, named DHPM1 and DHPM6, which demonstrated larvicide and repellentactivity against Anopheles arabiensis, to interact with artificial modelmembranes. The effects on the microviscosity of dpPC liposomes and on themechanical properties of dpPC monomolecular films were studied. In thiscontext, both compounds were able to modify the membrane microviscosity measureby fluorescence anisotropy of DPH and TMA-DPH. The DHPMs decreased the membrane fluidity at different depths and atdifferent membrane phase states, as revealed by for both fluorescent probes, beingthis effect more noticeable with TMA-DPH probe. This effect seems to indicate thatthe presence of DHPMs between lipid molecules would induce an enhancement ofthe intermolecular interaction, increasing the molecular order throughout thebilayer thickness. The compressionisotherms (π/A isotherms) performed in the presence of DHPMs inthe subphase, indicated that both compounds were able to modify the interfacialcharacteristics of dpPC, causing the expansion of the monolayer. Thecompressibility modulus were calculated and clearly showed that DHPMs inducedthe disappearance of dpPC phase transition, and the reduction of the elasticityof LC phase. Moreover, both compoundsshowed ability to penetrate in lipid monolayers with a πcutoff= 37 mN/m, indicating thatthe both compounds are able to penetrate in natural membranes. The resultsindicate that the DHPMs studied are clearly able to interact with membranes andmodify their properties.