Design and synthesis of new adamantyl-substituted antileishmanial ether phospholipids.
A series of new 2-[3-(2-alkyloxy-ethyl)-adamantan-1-yl]-ethoxy substituted ether phospholipids was synthesized and their antileishmanial activity was evaluated against Leishmania infantum amastigotes. The majority of the new analogues were significantly less cytotoxic than miltefosine while, antiparasitic activity depended on the length of the 2-alkyloxy substituent. The most potent compounds were {2-[[[3-(2-hexyloxy-ethyl)-adamant-1-yl]-ethoxy]hydroxyphosphinyloxy]ethyl}-Nu,Nu,Nu-trimethyl-ammonium inner salt (5b) and {2-[[[3-(2-octyloxy-ethyl)-adamant-1-yl]-ethoxy]hydroxyphosphinyloxy]ethyl}-Nu,Nu,Nu-trimethyl-ammonium inner salt (5c).
Papanastasiou
Ioannis
I
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, Athens 15771, Greece.
Prousis
Kyriakos C
KC
Georgikopoulou
Kalliopi
K
Pavlidis
Theofilos
T
Scoulica
Effie
E
Kolocouris
Nicolas
N
Calogeropoulou
Theodora
T
D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D006801:Humans; D018314:Leishmania infantum / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects; D010742:Phospholipid Ethers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology
D000981:Antiprotozoal Agents; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C039128:miltefosine