Bisphosphonic acids and related compounds as inhibitors of nucleotide- and polyphosphate-processing enzymes: A PPK1 and PPK2 case study
Research output: Contribution to journal › Article › peer-review
Electronic versions
DOI
Bisphosphonic acids, which are structural analogs of pyrophosphate, constitute a class of compounds with very high potential for the construction of effective inhibitors of enzymes operating on oligo- and polyphosphates. The bisphosphonate-based methodology was applied for the discovery of inhibitors of two families of polyphosphate kinases (PPK1 and PPK2). Screening of thirty-two structurally diverse bisphosphonic acids and related compounds revealed several micromolar inhibitors of both enzymes. Importantly, selectivity of bisphosphonates could be achieved by application of the appropriate side chain.
Keywords
- Diphosphonates/pharmacology, Enzyme Inhibitors/pharmacology, Isoenzymes/antagonists & inhibitors, Nucleotides/metabolism, Phosphotransferases (Phosphate Group Acceptor)/antagonists & inhibitors, Polyphosphates/metabolism
| Original language | English |
|---|---|
| Pages (from-to) | 1197-1206 |
| Number of pages | 10 |
| Journal | Chemical biology & drug design |
| Volume | 93 |
| Issue number | 6 |
| Early online date | 28 Nov 2018 |
| DOIs | |
| Publication status | Published - 1 Jun 2019 |
| Externally published | Yes |