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Institute of Organic Chemistry
and Biochemistry of the CAS

Take the step towards a career in organic chemistry and biochemistry...


All publications
Metallacarborane Sulfamides: Unconventional, Specific, and Highly Selective Inhibitors of Carbonic Anhydrase IX
Metallacarborane Sulfamides: Unconventional, Specific, and Highly Selective Inhibitors of Carbonic Anhydrase IX
B. Grüner
Jiří Brynda
V. Das
V. Šícha
J. Štěpánková
J. Nekvinda
J. Holub
Klára Pospíšilová
M. Fábry
Petr Pachl
V. Král
Michael Kugler
V. Mašek
M. Medvedíková
Stanislava Matějková
A. Nová
B. Lišková
S. Gurská
P. Džubák
M. Hajdúch
Pavlína Řezáčová
Journal of Medicinal Chemistry 62 (21): 9560-9575 (2019).
Carbonic anhydrase IX (CAIX) is a transmembrane enzyme that regulates pH in hypoxic tumors and promotes tumor cell survival. Its expression is associated with the occurrence of metastases and poor prognosis. Here, we present nine derivatives of the cobalt bis(dicarbollide)(1−) anion substituted at the boron or carbon sites by alkysulfamide group(s) as highly specific and selective inhibitors of CAIX. Interactions of these compounds with the active site of CAIX were explored on the atomic level using protein crystallography. Two selected derivatives display subnanomolar or picomolar inhibition constants and high selectivity for the tumor-specific CAIX over cytosolic isoform CAII. Both derivatives had a time-dependent effect on the growth of multicellular spheroids of HT-29 and HCT116 colorectal cancer cells, facilitated penetration and/or accumulation of doxorubicin into spheroids, and displayed low toxicity and showed promising pharmacokinetics and a significant inhibitory effect on tumor growth in syngenic breast 4T1 and colorectal HT-29 cancer xenotransplants.
A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy
Aisylu Gaifullina
Joanna Lazniewska
E. V. Gerasimova
F. Gulshat
G. F. Burkhanova
Yuriy Rzhepetskyy
Andriy Tomin
Paula Rivas-Ramirez
J. Huang
Leoš Cmarko
G. W. Zamponi
G. F. Sitdikova
Norbert Weiss
Pain 160 (12): 2798-2810 (2019).
Prolactin-releasing peptide: Physiological and pharmacological properties
Veronika Pražienková
Andrea Popelová
Jaroslav Kuneš
Lenka Maletínská
International Journal of Molecular Sciences 20 (21): 5297 (2019).

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