Amphiphilic Nature of New Antitubercular Drug Candidates and Their Interaction With Lipid Monolayer

  • K. Hill
  • C. B. Pénzes
  • B. G. Vértessy
  • Z. Szabadka
  • V. Grolmusz
  • É. Kiss
Conference paper
Part of the Progress in Colloid and Polymer Science book series (PROGCOLLOID, volume 135)


Tuberculosis remains a major problem throughout the world causing large number of deaths, more than that from any other single infectious disease [1]. 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 [2]. Introduction of new in silico identified drug candidates which are expected to be specific inhibitor of dUTPase [3] 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.

Langmuir monolayer Lipid affinity Membrane model Penetration of drug Surface activity 


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  1. 1.
    Raja A (2004) Indian J Med Res 120:213 Google Scholar
  2. 2.
    Kaufmann SHE (2004) Ann Rheum Dis 63:50 CrossRefGoogle Scholar
  3. 3.
    Chan S, Segelke B, Lekin T, Krupka H, Cho US, Kim M, So M, Kim CY, Naranjo CM, Rogers YC, Park MS, Waldo GS, Pashkov I, Cascio D, Perry JL, Sawaya MR (2004) J Mol Biol 341:503 CrossRefGoogle Scholar
  4. 4.
    World Health Organization (2002) Report 2002 Google Scholar
  5. 5.
    Chimote G, Banerjee R (2005) Respir Physiol Neurobiol 145:65 CrossRefGoogle Scholar
  6. 6.
    Tripathi RP, Tewari N, Dwivedi N, Tiwari VK (2004) Med Res Rev 25:93 CrossRefGoogle Scholar
  7. 7.
    Barabás O, Pongrácz V, Kovári J, Wilmanns M, Vértessy BG (2004) J Biol Chem 279:42907 CrossRefGoogle Scholar
  8. 8.
    Varga B, Migliardo F, Takacs E, Vértessy BG, Magazù S, Mondelli C (2008) J Chem Phys 345:250 CrossRefGoogle Scholar
  9. 9.
    Varga B, Migliardo F, Takacs E, Vértessy BG, Magazù S (2008) J Mol Struct 886:128 CrossRefGoogle Scholar
  10. 10.
    MacRitchie F (1990) Chemistry of Interfaces. Academic Press, San Diego Google Scholar
  11. 11.
    Brezesinski G, Möhwald H (2003) Adv Colloid Interf Sci 100–102:563 CrossRefGoogle Scholar
  12. 12.
    Maget-Dana R (1999) Biochem Biophys Acta 1462:109 CrossRefGoogle Scholar
  13. 13.
    Deleu M, Paquot M, Nylander T (2005) J Colloid Interf Sci 283:358 CrossRefGoogle Scholar
  14. 14.
    Hardy NJ, Richardson TH, Grunfeld F (2006) Colloid Surf A 284–285:202 CrossRefGoogle Scholar
  15. 15.
    Kiss É, Varga A, Vargha-Butler E (2004) Phys Chem Chem Phys 6:1575 CrossRefGoogle Scholar
  16. 16.
    Jablonowska E, Bilewicz R (2007) Thin Solid Films 515:3962 CrossRefGoogle Scholar
  17. 17.
    Fa N, Ronkart S, Schanck A, Deleu M, Gaigneaux A, Goormaghtigh E, Mingeot-Leclercq MP (2006) Chem Phys Lipids 144:108 CrossRefGoogle Scholar
  18. 18.
    Pickholz M, Oliveira ON JR, Skaf MS (2007) Biophys Chem 125:425 CrossRefGoogle Scholar
  19. 19.
    Zhao L, Feng SS (2006) J Colloid Interf Sci 300:314 CrossRefGoogle Scholar
  20. 20.
    Hac-Wydro K, Dynarowicz-Latka P, Grzybowska J, Borowski E (2005) Biophys Chem 116:77 CrossRefGoogle Scholar
  21. 21.
    Serrano AG, Perez-Gil J (2006) Chem Phys Lipids 141:105 CrossRefGoogle Scholar
  22. 22.
    Minones J Jr, Gomez-Serranillos IR, Conde O, Dynarowicz-Latka P (2006) J Colloid Interf Sci 301:258 CrossRefGoogle Scholar
  23. 23.
    Varga B, Barabas O, Takacs E, Vértessy BG (2008) Biochem Biophys Res Commun 373:8 CrossRefGoogle Scholar
  24. 24.
    Takácsné Novák K, Völgyi G (2005) Magy Kém Foly 4:169 Google Scholar
  25. 25.
    Rotenberg Y, Boruvka L, Neumann AW (1983) J Colloid Interf Sci 93:169 CrossRefGoogle Scholar
  26. 26.
    Miller R, Sedev M, Schano KH, Ng C, Neumann AW (1993) Colloid Surf A 69:209 CrossRefGoogle Scholar
  27. 27.
    Miller R, Policova Z, Sedev R, Neumann AW (1993) Colloid Surf A 76:179 CrossRefGoogle Scholar
  28. 28.
    Hill K, Horváth-Szanics E, Hajós G, Kiss É (2008) Colloid Surf A 319:180 CrossRefGoogle Scholar
  29. 29.
    Irwin JJ, Shoichet KB (2004) J Chem Inf Model 45:177 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • K. Hill
    • 1
  • C. B. Pénzes
    • 1
  • B. G. Vértessy
    • 2
  • Z. Szabadka
    • 3
    • 4
  • V. Grolmusz
    • 3
    • 4
  • É. Kiss
    • 1
  1. 1.Laboratory of Interfaces and Nanostructures, Institute of ChemistryEötvös UniversityBudapest 112Hungary
  2. 2.Institute of EnzymologyHungarian Academy of SciencesBudapestHungary
  3. 3.Protein Information Technology Group, Institute of MathematicsEötvös UniversityBudapestHungary
  4. 4.Uratim Ltd.NyíregyházaHungary

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