title: 3D-Quantitative structure-activity relationships of synthetic antileishmanial ring-substituted ether phospholipids.
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.
authors.affiliation: Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vas. Constantinou Av., 116 35 Athens, Greece.
authors.forename: Agnes
authors.initials: A
authors.lastname: Kapou
authors.forename: Nikolas P
authors.initials: NP
authors.lastname: Benetis
authors.forename: Nikos
authors.initials: N
authors.lastname: Avlonitis
authors.forename: Theodora
authors.initials: T
authors.lastname: Calogeropoulou
authors.forename: Maria
authors.initials: M
authors.lastname: Koufaki
authors.forename: Efi
authors.initials: E
authors.lastname: Scoulica
authors.forename: Sotiris S
authors.initials: SS
authors.lastname: Nikolaropoulos
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
mesh_terms: D000818:Animals; D015195:Drug Design; D007893:Leishmania donovani / Q000187:drug effects*; D018314:Leishmania infantum / Q000187:drug effects*; D008958:Models, Molecular; D010742:Phospholipid Ethers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D010742:Phospholipid Ethers; D014344:Trypanocidal Agents