CS
Pavlína Maloy Řezáčová

Pavlína Maloy Řezáčová

mail pavlina.rezacovainvalid-email-name@invalid-email-domainuochb.cas.cz
phone +420 220 183 144
Group leader
Pavlína Maloy Řezáčová Group
Structural Biology
All publications

Selected papers

Sulfonamido carboranes as highly selective inhibitors of cancer-specific carbonic anhydrase IX
Sulfonamido carboranes as highly selective inhibitors of cancer-specific carbonic anhydrase IX
J. Štěpánková M. Kugler J. Holub V. Šícha V. Das J. Nekvinda S. El Anwar M. Havránek K. Pospíšilová M. Fábry V. Král M. Medvedíková S. Matějková B. Lišková S. Gurská P. Džubák J. Brynda M. Hajdúch B. Grüner P. Řezáčová
European Journal of Medicinal Chemistry 200: 112460 (2020)
Carbonic anhydrase IX (CA IX) is a transmembrane enzyme overexpressed in hypoxic tumors, where it plays an important role in tumor progression. Specific CA IX inhibitors potentially could serve as anti-cancer drugs. We designed a series of sulfonamide inhibitors containing carborane clusters based on prior structural knowledge of carborane binding into the enzyme active site. Two types of carborane clusters, 12-vertex dicarba-closo-dodecaborane and 11-vertex 7,8-dicarba-nido-undecaborate (dicarbollide), were connected to a sulfonamide moiety via aliphatic linkers of varying lengths (1–4 carbon atoms; n = 1–4). In vitro testing of CA inhibitory potencies revealed that the optimal linker length for selective inhibition of CA IX was n = 3. A 1-sulfamidopropyl-1,2-dicarba-closo-dodecaborane (3) emerged as the strongest CA IX inhibitor from this series, with a Ki value of 0.5 nM and roughly 1230-fold selectivity towards CA IX over CA II. X-ray studies of 3 yielded structural insights into…
Go to the publication arrow
All publications

Latest publications

3H-Pyrazolo[4,3-f]quinoline-Based Kinase Inhibitors Inhibit the Proliferation of Acute Myeloid Leukemia Cells In Vivo
N. Dayal E. Řezníčková D. E. Hernandez M. Peřina S. Torregrosa-Allen B. D. Elzey J. Škerlová H. Ajani S. Djukic V. Vojáčková M. Lepšík P. Řezáčová V. Kryštof R. Jorda H. O. Sintim
Journal of Medicinal Chemistry 64 (15): 10981–10996 (2021)
Go to the publication arrow
Mialostatin, a Novel Midgut Cystatin from Ixodes ricinus Ticks: Crystal Structure and Regulation of Host Blood Digestion
J. Kotál M. Buša V. Urbanová P. Řezáčová J. Chmelař H. Langhansová D. Sojka M. Mareš M. Kotsyfakis
International Journal of Molecular Sciences 22 (11): 5371 (2021)
Go to the publication arrow
Re-emerging Aspartic Protease Targets: Examining Cryptococcus neoformans Major Aspartyl Peptidase 1 as a Target for Antifungal Drug Discovery
R. Kryštůfek P. Šácha J. Starková J. Brynda M. Hradilek E. Tloušťová J. Grzymska W. Rut M. J. Boucher M. Drag P. Majer M. Hájek P. Řezáčová H. D. Madhani C. S. Craik J. Konvalinka
Journal of Medicinal Chemistry 64 (10): 6706–6719 (2021)
Go to the publication arrow
Druggable Hot Spots in the Schistosomiasis Cathepsin B1 Target Identified by Functional and Binding Mode Analysis of Potent Vinyl Sulfone Inhibitors
A. Jílková P. Rubešová J. Fanfrlík P. Fajtová P. Řezáčová J. Brynda M. Lepšík H. Mertlíková-Kaiserová C. D. Emal A. R. Renslo W. R. Roush M. Horn C. R. Caffrey M. Mareš
ACS Infectious Diseases 7 (5): 1077–1088 (2021)
Go to the publication arrow