TY  - JOUR
AU  - Sibinčić, Nikolina
AU  - Kalinin, Stanislav
AU  - Sharoyko, Vladimir
AU  - Efimova, Julia
AU  - Gasilina, Olga
AU  - Korsakov, Mikhail
AU  - Gureev, Maxim
AU  - Krasavin, Mikhail
PY  - 2023
UR  - http://cherry.chem.bg.ac.rs/handle/123456789/6049
AB  - Abstract: Aims: To synthesize novel sulfonamide inhibitors of carbonic anhydrase and develop in vitro prioritization workflow to select compounds for in vivo evaluation.
Background: Carbonic anhydrase (CA) inhibitors gain significant attention in the context of drug discovery research for glaucoma, hypoxic malignancies, and bacterial infections. In previous works, we have successfully used direct sulfochlorination approach to develop diverse heterocyclic primary sulfonamides with remarkable activity and selectivity against therapeutically relevant CA isoforms.
Objective: Synthesis and investigation of the CA inhibitory properties of novel trifluoromethylisoxa- zolyl- and trifluoromethylpyrazolyl-substituted (hetero)aromatic sulfonamides.
Methods: Thirteen trifluoromethylisoxazolyl- and thirteen trifluoromethylpyrazolyl-substituted (het-
ero)aromatic sulfonamides were synthesized by direct sulfochlorination of hydroxyisoxazolines and
pyrazoles followed by reaction with ammonia. The compound structures were confirmed by 1H and
13
C NMR as well as element analysis. The obtained compounds were evaluated, using the CA es-
terase activity assay, for their potential to block the catalytic activity of bovine CA (bCA).
Results: Eight most potent compounds selected based on the esterase activity assay data were tested
for direct affinity to the enzyme using the thermal shift assay (TSA). These compounds displayed Kd values (measured by TSA) in the double-digit nanomolar range, thus showing comparable activity to the reference drug acetazolamide.
PB  - Bentham Science Publishers
T2  - Medicinal Chemistry
T1  - A Series of Trifluoromethylisoxazolyl- and Trifluoromethylpyrazolyl- Substituted (Hetero)aromatic Sulfonamide Carbonic Anhydrase Inhibitors: Synthesis, and Convenient Prioritization Workflow for Further In Vivo Studies
VL  - 19
IS  - 2
SP  - 193
EP  - 210
DO  - 10.2174/1573406418666220831112049
ER  - 

@article{
author = "Sibinčić, Nikolina and Kalinin, Stanislav and Sharoyko, Vladimir and Efimova, Julia and Gasilina, Olga and Korsakov, Mikhail and Gureev, Maxim and Krasavin, Mikhail",
year = "2023",
abstract = "Abstract: Aims: To synthesize novel sulfonamide inhibitors of carbonic anhydrase and develop in vitro prioritization workflow to select compounds for in vivo evaluation.
Background: Carbonic anhydrase (CA) inhibitors gain significant attention in the context of drug discovery research for glaucoma, hypoxic malignancies, and bacterial infections. In previous works, we have successfully used direct sulfochlorination approach to develop diverse heterocyclic primary sulfonamides with remarkable activity and selectivity against therapeutically relevant CA isoforms.
Objective: Synthesis and investigation of the CA inhibitory properties of novel trifluoromethylisoxa- zolyl- and trifluoromethylpyrazolyl-substituted (hetero)aromatic sulfonamides.
Methods: Thirteen trifluoromethylisoxazolyl- and thirteen trifluoromethylpyrazolyl-substituted (het-
ero)aromatic sulfonamides were synthesized by direct sulfochlorination of hydroxyisoxazolines and
pyrazoles followed by reaction with ammonia. The compound structures were confirmed by 1H and
13
C NMR as well as element analysis. The obtained compounds were evaluated, using the CA es-
terase activity assay, for their potential to block the catalytic activity of bovine CA (bCA).
Results: Eight most potent compounds selected based on the esterase activity assay data were tested
for direct affinity to the enzyme using the thermal shift assay (TSA). These compounds displayed Kd values (measured by TSA) in the double-digit nanomolar range, thus showing comparable activity to the reference drug acetazolamide.",
publisher = "Bentham Science Publishers",
journal = "Medicinal Chemistry",
title = "A Series of Trifluoromethylisoxazolyl- and Trifluoromethylpyrazolyl- Substituted (Hetero)aromatic Sulfonamide Carbonic Anhydrase Inhibitors: Synthesis, and Convenient Prioritization Workflow for Further In Vivo Studies",
volume = "19",
number = "2",
pages = "193-210",
doi = "10.2174/1573406418666220831112049"
}

Sibinčić, N., Kalinin, S., Sharoyko, V., Efimova, J., Gasilina, O., Korsakov, M., Gureev, M.,& Krasavin, M.. (2023). A Series of Trifluoromethylisoxazolyl- and Trifluoromethylpyrazolyl- Substituted (Hetero)aromatic Sulfonamide Carbonic Anhydrase Inhibitors: Synthesis, and Convenient Prioritization Workflow for Further In Vivo Studies. in Medicinal Chemistry
Bentham Science Publishers., 19(2), 193-210.
https://doi.org/10.2174/1573406418666220831112049

Sibinčić N, Kalinin S, Sharoyko V, Efimova J, Gasilina O, Korsakov M, Gureev M, Krasavin M. A Series of Trifluoromethylisoxazolyl- and Trifluoromethylpyrazolyl- Substituted (Hetero)aromatic Sulfonamide Carbonic Anhydrase Inhibitors: Synthesis, and Convenient Prioritization Workflow for Further In Vivo Studies. in Medicinal Chemistry. 2023;19(2):193-210.
doi:10.2174/1573406418666220831112049 .

Sibinčić, Nikolina, Kalinin, Stanislav, Sharoyko, Vladimir, Efimova, Julia, Gasilina, Olga, Korsakov, Mikhail, Gureev, Maxim, Krasavin, Mikhail, "A Series of Trifluoromethylisoxazolyl- and Trifluoromethylpyrazolyl- Substituted (Hetero)aromatic Sulfonamide Carbonic Anhydrase Inhibitors: Synthesis, and Convenient Prioritization Workflow for Further In Vivo Studies" in Medicinal Chemistry, 19, no. 2 (2023):193-210,
https://doi.org/10.2174/1573406418666220831112049 . .