?Membrane interaction of dihydropyrimidines?

MARIELA SÁNCHEZ; MARIANI, ELISA; KATHARIGATTA VENUGOPALA; ODHAV BARTHI; GLEISER RAQUEL; DANIEL GARCÍA

Santiago del Estero

Congreso; XLIV Reunion Anual de la Sociedad Argentina de Biofisica (SAB); 2015

Sociedad Argentina de Biofísica

Dihydropyrimidines (DHPMs) derivatives have a signficant role in medicinal chemistry for various pharmacological activities, such as anticancer, antibacterial, antifungal, antihypertensive, antitubercular, antimalarial, antiviral, and anti-inflammatory activities. The high hydrophobicity of DHPMs permits to suppose that many of these effects could involve their interaction with biological membranes. The purpose of the present study was to determine the ability of two DHPM analogs, named DHPM1 and DHPM6, which demonstrated larvicide and repellent activity against Anopheles arabiensis, to interact with artificial model membranes. The effects on the microviscosity of dpPC liposomes and on the mechanical properties of dpPC monomolecular films were studied. In this context, both compounds were able to modify the membrane microviscosity measure by fluorescence anisotropy of DPH and TMA-DPH. The DHPMs decreased the membrane fluidity at different depths and at different membrane phase states, as revealed by for both fluorescent probes, being this effect more noticeable with TMA-DPH probe. This effect seems to indicate that the presence of DHPMs between lipid molecules would induce an enhancement of the intermolecular interaction, increasing the molecular order throughout the bilayer thickness. The compression isotherms (π/A isotherms) performed in the presence of DHPMs in the subphase, indicated that both compounds were able to modify the interfacial characteristics of dpPC, causing the expansion of the monolayer. The compressibility modulus were calculated and clearly showed that DHPMs induced the disappearance of dpPC phase transition between LE and LC states, and the reduction of the elasticity of condensed phases (LC). Moreover, both compounds showed ability to penetrate in lipid monolayers with a πcutoff= 37 mN/m, indicating that the both compounds are able to penetrate in natural membranes. The results indicate that the DHPMs studied are clearly able to interact with membranes and modify their properties.Acknowledgements: This work was supported by grants from SECyT-UNC, FONCYT-MinCyT and CONICET, Argentina.