Journal article
Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl diphosphate synthase and bone resorption
Journal of medicinal chemistry, Vol.48(8), pp.2957-2963
2005
DOI: 10.1021/jm040209d
PMID: 15828834
Abstract
We report the design, synthesis and testing of a series of novel bisphosphonates, pyridinium-1-yl-hydroxy-bisphosphonates, based on the results of comparative molecular similarity indices analysis and pharmacophore modeling studies of farnesyl diphosphate synthase (FPPS) inhibition, human Vgamma2Vdelta2 T cell activation and bone resorption inhibition. The most potent molecules have high activity against an expressed FPPS from Leishmania major, in Dictyostelium discoideum growth inhibition, in gammadelta T cell activation and in an in vitro bone resorption assay. As such, they represent useful new leads for the discovery of new bone resorption, antiinfective and anticancer drugs.
Details
- Title: Subtitle
- Pyridinium-1-yl bisphosphonates are potent inhibitors of farnesyl diphosphate synthase and bone resorption
- Creators
- John M SANDERS - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesYONGCHENG SONG - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesGary A MEINTS - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesAurora Ortiz GOMEZ - López-Neyra Institute of Parasitology and Biomedicine, CSIC, Granada, SpainDolores GONZALEZ-PACANOWSKA - López-Neyra Institute of Parasitology and Biomedicine, CSIC, Granada, SpainAmy M RAKER - Department of Internal Medicine and the Interdisciplinary Group in Immunology, University of Iowa, EMRB 340F, Iowa City, Iowa 52242, United StatesHONG WANG - Department of Internal Medicine and the Interdisciplinary Group in Immunology, University of Iowa, EMRB 340F, Iowa City, Iowa 52242, United StatesErmond R VAN BEEK - Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, NetherlandsSocrates E PAPAPOULOS - Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, NetherlandsCraig T MORITA - Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, NetherlandsEric OLDFIELD - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesJulian M. W CHAN - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesYONGHUI ZHANG - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesSamuel JENNINGS - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesThomas KOSZTOWSKI - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesSarah ODEH - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesRyan FLESSNER - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesChristine SCHWERDTFEGER - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United StatesEvangelia KOTSIKOROU - Department of Chemistry, 600 South Mathews Avenue, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States
- Resource Type
- Journal article
- Publication Details
- Journal of medicinal chemistry, Vol.48(8), pp.2957-2963
- DOI
- 10.1021/jm040209d
- PMID
- 15828834
- NLM abbreviation
- J Med Chem
- ISSN
- 0022-2623
- eISSN
- 1520-4804
- Publisher
- American Chemical Society
- Language
- English
- Date published
- 2005
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094595402771
Metrics
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