3D-Quantitative structure-activity relationships of synthetic antileishmanial ring-substituted ether phospholipids.
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.
Kapou
Agnes
A
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vas. Constantinou Av., 116 35 Athens, Greece.
Benetis
Nikolas P
NP
Avlonitis
Nikos
N
Calogeropoulou
Theodora
T
Koufaki
Maria
M
Scoulica
Efi
E
Nikolaropoulos
Sotiris S
SS
Mavromoustakos
Thomas
T
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
D010742:Phospholipid Ethers; D014344:Trypanocidal Agents