Solid-phase synthesis and bioevaluation of lupeol-based libraries as antimalarial agents.
The use of the triterpenoid lupeol as a scaffold for the synthesis of lupeol-based libraries is described. Lupeol was anchored to a solid support (Rink amide/Sieber Amide) through aliphatic dicarboxylic acid moieties, which also served as a site for introducing diversity. The resulting polymer linked 3beta-O (resin-alkanoyl)-lup-20(29)-ene 3 was used to generate key intermediates 3beta-O (resin-alkanoyl)-30-bromo-lup-20(29)-ene 4 and 3beta-O (resin-alkanoyl)-30-amino-lup-20(29)-ene 6 for the generation of libraries based on disubstituted lupeol derivatives. A 96-member library was screened for its in-vitro antimalarial activity against Plasmodium falciparum.
Srinivasan
T
T
Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India.
Srivastava
G K
GK
Pathak
A
A
Batra
S
S
Raj
K
K
Singh
Kshipra
K
Puri
S K
SK
Kundu
B
B
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D053978:Pentacyclic Triterpenes; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D016339:Spectrometry, Mass, Fast Atom Bombardment; D014315:Triterpenes / Q000737:chemistry*; D000094042:Lupanes
D000962:Antimalarials; D007202:Indicators and Reagents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C010480:lupeol; D000094042:Lupanes