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Inhibitors of CA IX Enzyme Based on Polyhedral Boron Compounds
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SYSNO ASEP 0543164 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Inhibitors of CA IX Enzyme Based on Polyhedral Boron Compounds Author(s) Kugler, Michael (UOCHB-X) RID, ORCID
Nekvinda, Jan (UACH-T) RID, SAI, ORCID
Holub, Josef (UACH-T) SAI, RID, ORCID
El Anwar, Suzan (UACH-T) SAI, ORCID, RID
Das, V. (CZ)
Šícha, Václav (UACH-T) RID, ORCID, SAI
Pospíšilová, Klára (UOCHB-X)
Fábry, M. (CZ)
Král, V. (CZ)
Brynda, Jiří (UOCHB-X) RID, ORCID
Kašička, Václav (UOCHB-X) RID, ORCID
Hajdúch, M. (CZ)
Řezáčová, Pavlína (UOCHB-X) RID, ORCID
Grüner, Bohumír (UACH-T) RID, SAI, ORCIDSource Title Chembiochem. - : Wiley - ISSN 1439-4227
Roč. 22, č. 18 (2021), s. 2741-2761Number of pages 21 s. Language eng - English Country DE - Germany Keywords carbonic anhydrase ; carborane ; cobalt bis(dicarbollide) ; crystallography ; enzyme inhibition ; SAR studies OECD category Organic chemistry R&D Projects GA18-27648S GA ČR - Czech Science Foundation (CSF) TE01020028 GA TA ČR - Technology Agency of the Czech Republic (TA ČR) LM2015064 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support UOCHB-X - RVO:61388963 ; UACH-T - RVO:61388980 UT WOS 000655741200001 EID SCOPUS 85106591700 DOI 10.1002/cbic.202100121 Annotation 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 Zn2+ 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). Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2022 Electronic address https://doi.org/10.1002/cbic.202100121
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