Membrane interaction of Dihydropyrimidines

MARIELA SANCHEZ-BORZONE; MARIA E MARIANI; KATHARIGATTA VENUGOPALA. N.; BARTHI ODHAV; GLEISER RAQUEL; DANIEL A. GARCIA

SALTO

Congreso; Latin American Crosstalk in Biophysics and Physiology 2015; 2015

Sociedad Argentina de Biofísica y Seccional Biofísica de la Sociedad Uruguaya de Biociencias

Dihydropyrimidines (DHPMs) derivatives have a signficant role inmedicinal chemistry for various pharmacological activities, such asanticancer, antibacterial, antifungal, antihypertensive, antitubercular,antimalarial, antiviral, and anti-inflammatory activities. The highhydrophobicity of DHPMs suggests that many of these effects couldinvolve their interaction with biological membranes modulating thesupramolecular organization of the substrate summarized in the concept of?interfacial quality?. The purpose of the present study was to determine theability of two DHPM analogs, -1 and -6, which demonstrated larvicide andrepellent activity against Anopheles arabiensis, to interact with artificialmodel membranes. The effects on the microviscosity of dpPC liposomesand on the properties of dpPC monomolecular films were studied. In thiscontext, both compounds were able to modify the membrane microviscositymeasure by fluorescence anisotropy of DPH and TMA-DPH. The DHPMsdecreased the membrane fluidity at different depths and at differentmembrane phase states, as revealed by both fluorescent probes. This effectwas more noticeable with TMA-DPH indicating that the presence ofDHPMs between lipid molecules would induce an enhancement of theintermolecular interaction, increasing the molecular order throughout thebilayer thickness. The compression isotherms (π/A isotherms) performed inthe presence of DHPMs in the subphase, indicated that both compoundswere able to modify the interfacial characteristics of dpPC, causing theexpansion of the monolayer. The compressibility modulus clearly showedthat DHPMs induced the disappearance of dpPC phase transition betweenLE and LC states and the reduction of the elasticity of condensed phases(LC). Moreover, both compounds showed ability to penetrate in lipidmonolayers with a πcut-off= 37 mN/m, indicating that both compounds areable to penetrate natural membranes and modify their properties.Acknowledgements: This work was supported by grants fro SECyT-UNC, FONCYT-MinCyTand CONICET.