Abstract
Apicidin's indole was efficiently converted into a series of N-substituted quinolone derivatives by indole N-alkylation followed by a two-step, one-pot, ozonolysis/aldol condensation protocol. The new quinolones exhibited good parasite selectivity and potency both at the level of their molecular target, histone deacetylase, and in their whole cell antiproliferative activity in vitro.
MeSH terms
-
Animals
-
Antimalarials / chemical synthesis
-
Antimalarials / chemistry
-
Antimalarials / pharmacology
-
Antiprotozoal Agents / chemical synthesis*
-
Antiprotozoal Agents / chemistry
-
Antiprotozoal Agents / pharmacology
-
Binding, Competitive
-
Cell Division / drug effects
-
Cell Extracts
-
Chickens
-
Eimeria tenella / cytology
-
Eimeria tenella / drug effects
-
Eimeria tenella / metabolism
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology
-
HeLa Cells
-
Histone Deacetylase Inhibitors*
-
Histone Deacetylases / metabolism
-
Humans
-
In Vitro Techniques
-
Indoles / chemical synthesis*
-
Indoles / chemistry
-
Indoles / pharmacology
-
Liver / metabolism
-
Peptides, Cyclic / chemistry*
-
Plasmodium falciparum / drug effects
-
Quinolones / chemical synthesis*
-
Quinolones / chemistry
-
Quinolones / pharmacology
-
Structure-Activity Relationship
Substances
-
Antimalarials
-
Antiprotozoal Agents
-
Cell Extracts
-
Enzyme Inhibitors
-
Histone Deacetylase Inhibitors
-
Indoles
-
Peptides, Cyclic
-
Quinolones
-
apicidin
-
Histone Deacetylases