Membrane Affinity of New Antitubercular Drug Candidates Using a Phospholipid Langmuir Monolayer Model and LB Technique

摘要

Tuberculosis is a major problem throughout the world causing 1.9 million deaths annually, and induces a major global public health problem. The pathogen responsible for the disease is Mycobacterium tuberculosis. Drug candidates expected to be specific inhibitors of dUTPase an essential enzyme of Mycobacterium tuberculosis were identified in silico. A phospholipid Langmuir monolayer formed at the liquid/air interface as a simple but versatile model of the cell membrane was applied to assess the membrane affinity of the drug candidates. The interaction of three different potential drug molecules TB501, TB502, and TB505 with lipid monolayer was characterised by tensiometry, and atomic force microscopy at different temperatures. The degree of penetration of drug candidates into the lipid film and the structural variation of drug penetrated lipid films revealed by atomic force microscopic images were compared.