Journal article
Impact of α-modifications on the activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors
Bioorganic & medicinal chemistry, Vol.44, pp.116307-116307
08/15/2021
DOI: 10.1016/j.bmc.2021.116307
PMCID: PMC8370032
PMID: 34298413
Abstract
[Display omitted]
Agents that inhibit the enzyme geranylgeranyl diphosphate synthase (GGDPS) have anti-cancer activity and our prior studies have investigated the structure-function relationship for a family of isoprenoid triazole bisphosphonates as GGDPS inhibitors. To further explore this structure-function relationship, a series of novel α-modified triazole phosphonates was prepared and evaluated for activity as GGDPS inhibitors in enzyme and cell-based assays. These studies revealed flexibility at the α position of the bisphosphonate derivatives with respect to being able to accommodate a variety of substituents without significantly affecting potency compared to the parent unsubstituted inhibitor. However, the monophosphonate derivatives lacked activity. These studies further our understanding of the structure-function relationship of the triazole-based GGDPS inhibitors and lay the foundation for future studies evaluating the impact of α-modifications on in vivo activity.
Details
- Title: Subtitle
- Impact of α-modifications on the activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors
- Creators
- Alisa E.R Fairweather - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USADaniel B Goetz - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USAChloe M Schroeder - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USANazmul H Bhuiyan - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USAMichelle L Varney - Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USADavid F Wiemer - Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USASarah A Holstein - Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA
- Resource Type
- Journal article
- Publication Details
- Bioorganic & medicinal chemistry, Vol.44, pp.116307-116307
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.bmc.2021.116307
- PMID
- 34298413
- PMCID
- PMC8370032
- ISSN
- 0968-0896
- eISSN
- 1464-3391
- Language
- English
- Date published
- 08/15/2021
- Academic Unit
- Neuroscience and Pharmacology; Chemistry
- Record Identifier
- 9984216592102771
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