Interaction of heterocyclic drugs with proteins and biological membranes: spectroscopic studies

• Grant number: 96/00039-7
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 1996
• End date: August 31, 2000
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Marcel Tabak
• Grantee: Marcel Tabak
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Associated research grant(s): 98/00694-0 - The ph-dependent metalloporphyrin contrast agent aggregation on biological structures: a possible mechanism, AR.EXT; 97/13440-4 - Interaction of dipyridamole with anionic phospholipid vesicles fluorescence studies., AR.EXT; 97/05654-4 - Correaction of stern-volmer fluorescence quenching constants at very low optical absorption of the quencher., AR.EXT

Abstract

The main purpose of this project is the clarification of the molecular mechanisms of interactions of nitrogen heterocyclic drugs with proteins and biological membranes (model and natural). This is a relevant question both from the point of view of the therapeutic activity and as a biomimetic system. To reach this goal we will develop this study using different spectroscopic techniques that have been used in our laboratory in the past like fluorescence, optical absorption, NMR, EPR and circular dichroism. The class of nitrogen heterocyclic compounds comprises a broad range of substances: local anesthetics, tranquilizers, vasodilators, antimalaric drugs, porphyrins and metalloporphyrins. The biological effects of these drugs imply interactions with different tissue components. The interaction of charged and uncharged small molecules with membranes and proteins is probably one of the relevant events in the interaction drug-tissue at a molecular level. The understanding of the molecular mechanisms of these interactions is important both from the theoretical point of view and also from the practical one in the development of new drugs and in the selection of the most relevant drugs for different treatment schemes. The use of several spectroscopic techniques, each having advantages and limitations, allows one to obtain new data on the localization of the drug in the biological system and on the details of their interaction. (AU)