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Inhibitors of CA IX Enzyme Based on Polyhedral Boron Compounds.
- Source :
-
Chembiochem : a European journal of chemical biology [Chembiochem] 2021 Sep 14; Vol. 22 (18), pp. 2741-2761. Date of Electronic Publication: 2021 May 28. - Publication Year :
- 2021
-
Abstract
- This review describes recent progress in the design and development of inhibitors of human carbonic anhydrase IX (CA IX) based on space-filling carborane and cobalt bis(dicarbollide) clusters. CA IX enzyme is known to play a crucial role in cancer cell proliferation and metastases. The new class of potent and selective CA IX inhibitors combines the structural motif of a bulky inorganic cluster with an alkylsulfamido or alkylsulfonamido anchor group for Zn <superscript>2+</superscript> ion in the enzyme active site. Detailed structure-activity relationship (SAR) studies of a large series containing 50 compounds uncovered structural features of the cluster-containing inhibitors that are important for efficient and selective inhibition of CA IX activity. Preclinical evaluation of selected compounds revealed low toxicity, favorable pharmacokinetics and ability to reduce tumor growth. Cluster-containing inhibitors of CA IX can thus be considered as promising candidates for drug development and/or for combination therapy in boron neutron capture therapy (BNCT).<br /> (© 2021 Wiley-VCH GmbH.)
- Subjects :
- Binding Sites
Boron Compounds metabolism
Boron Compounds therapeutic use
Carbonic Anhydrase IX metabolism
Carbonic Anhydrase Inhibitors chemical synthesis
Carbonic Anhydrase Inhibitors metabolism
Carbonic Anhydrase Inhibitors therapeutic use
Humans
Molecular Dynamics Simulation
Neoplasms drug therapy
Organometallic Compounds chemistry
Structure-Activity Relationship
Sulfonamides chemistry
Boron Compounds chemistry
Carbonic Anhydrase IX antagonists & inhibitors
Carbonic Anhydrase Inhibitors chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1439-7633
- Volume :
- 22
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Chembiochem : a European journal of chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 33939874
- Full Text :
- https://doi.org/10.1002/cbic.202100121