2. Academic Validation
  3. 3D-Quantitative structure-activity relationships of synthetic antileishmanial ring-substituted ether phospholipids

3D-Quantitative structure-activity relationships of synthetic antileishmanial ring-substituted ether phospholipids

  • Bioorg Med Chem. 2007 Feb 1;15(3):1252-65. doi: 10.1016/j.bmc.2006.11.018.
Agnes Kapou 1,  Nikolas P Benetis,  Nikos Avlonitis,  Theodora Calogeropoulou,  Maria Koufaki,  Efi Scoulica,  Sotiris S Nikolaropoulos,  Thomas Mavromoustakos
Affiliations

Affiliation

  • 1 Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vas. Constantinou Av., 116 35 Athens, Greece.
PMID: 17158053 DOI: 10.1016/j.bmc.2006.11.018
Abstract

The application of 2D-NMR spectroscopy and Molecular Modeling in determining the active conformation of flexible molecules in 3D-QSAR was demonstrated in the present study. In particular, a series of 33 flexible synthetic Phospholipids, either 2-(4-alkylidene-cyclohexyloxy)ethyl- or omega-cycloalkylidene-substituted ether Phospholipids were systematically evaluated for their in vitro antileishmanial activity against the promastigote forms of Leishmania infantum and Leishmania donovani by CoMFA and CoMSIA 3D-QSAR studies. Steric and hydrophobic properties of the Phospholipids under study appear to govern their antileishmanial activity against both strains, while the electrostatic properties have no significant contribution. The acknowledgment of these important properties of the pharmacophore will aid in the rational design of new analogues with higher activity.

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