title: Triazole-based inhibitors of geranylgeranyltransferase II.
abstract: A small set of triazole bisphosphonates has been prepared and tested for the ability to inhibit geranylgeranyltransferase II (GGTase II). The compounds were prepared through use of click chemistry to assemble a central triazole that links a polar head group to a hydrophobic tail. The resulting compounds were tested for their ability to inhibit GGTase II in an in vitro enzyme assay and also were tested for cytotoxic activity in an MTT assay with the human myeloma RPMI-8226 cell line. The most potent enzyme inhibitor was the triazole with a geranylgeranyl tail, which suggests that inhibitors that can access the enzyme region that holds the isoprenoid tail will display greater activity.
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.forename: Sara V
authors.initials: SV
authors.lastname: Hartman
authors.forename: Ella J
authors.initials: EJ
authors.lastname: Born
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Smits
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Holstein
authors.forename: David F
authors.initials: DF
authors.lastname: Wiemer
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D057930:Click Chemistry; D004164:Diphosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D014166:Transferases; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004164:Diphosphonates; C095279:Rab geranylgeranyl transferase beta-subunit; D014230:Triazoles; D014166:Transferases; D019883:Alkyl and Aryl Transferases