Amphiphilic Nature of New Antitubercular Drug Candidates and Their Interaction With Lipid Monolayer
Tuberculosis remains a major problem throughout the world causing large number of deaths, more than that from any other single infectious disease . The treatment of the chronic inflammatory caused by Mycobacterium tuberculosis (Mtb) requires prolonged chemotherapy often associated with unwanted side effects and developing resistant bacterium strains . Introduction of new in silico identified drug candidates which are expected to be specific inhibitor of dUTPase  a vital enzyme of Mtb presents a novel approach in the combat with the disease. Three of those drug candidates – ligand 3, 4 and 69 – were compared in the present study considering their interfacial properties, polarity, amphipatic character and lipid affinity which are relevant in pharmaceutical function.
Langmuir monolayers were prepared from the ligands and their mixture with phospholipon as a simple model material of cell membrane. Analysis of the isotherms showed than ligand 3 and 44 presents significant affinity to the lipid building into the monolayer. The penetration ability of the drug candidates were also characterized by measuring the increase of surface pressure of the lipid monolayer following their injection to the subphase at two initial lipid densities. The results were in accordance with the order of log P app values determined for the three compounds as well as with their dynamic surface activity although the highest difference amongst the three ligands was observed in the penetration ability which is of paramount importance in the selection of promising therapeutic agent.
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