N-Oxide derivatives of 3-(3-pyridyl)-2-phosphonopropanoic acids as potential inhibitors of Rab geranylgeranylation.
The N-oxide derivatives of [2-(3-pyridinyl)-1-hydroxyethylidene-1,1-phosphonocarboxylic acid (or PEHPC) and [2-(3-pyridinyl)-1-ethylidene-1,1-phosphonocarboxylic acid (or PEPC) have been prepared and evaluated for their activity against several enzymes which utilize isoprenoids. The parent pyridines are known inhibitors of GGTase II, but the N-oxide derivatives show no improvement in biological activity in assays with the isolated enzyme. However, the PEHPC N-oxide did induce significant accumulation of intracellular light chain in myeloma cells, consistent with inhibition of Rab geranylgeranylation.
Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
Xiang
X
Zhou
Department of Internal Medicine, University of Iowa, Iowa City, IA 52242-1294, USA.
Ella J
EJ
Born
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Cheryl
C
Allen
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Sarah A
SA
Holstein
Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA. Electronic address: david-wiemer@uiowa.edu.
David F
DF
Wiemer
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D055808:Drug Discovery; D006801:Humans; D015394:Molecular Structure; D009101:Multiple Myeloma; D011422:Propionates / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011422:Propionates; D019883:Alkyl and Aryl Transferases; C075607:Rab geranylgeranyltransferase
Apoptosis; Bioassay; GGTase II; Myeloma; Pyridyl N-oxides; Rab GGTase