Anticonvulsant Effects of Carbonic Anhydrase Inhibitors: The Enigmatic Link Between Carbonic Anhydrases and Electrical Activity of the Brain

2021 ◽  
Author(s):  
Hatice Zehra Ozsoy
Keyword(s):  
Carbonic Anhydrase ◽  
Electrical Activity ◽  
Carbonic Anhydrases ◽  
Carbonic Anhydrase Inhibitors ◽  
The Brain ◽  
Anticonvulsant Effects

scholarly journals Carborane-Based Carbonic Anhydrase Inhibitors: Insight into CAII/CAIX Specificity from a High-Resolution Crystal Structure, Modeling, and Quantum Chemical Calculations

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Pavel Mader ◽  
Adam Pecina ◽  
Petr Cígler ◽  
Martin Lepšík ◽  
Václav Šícha ◽  
...  
Keyword(s):  
Crystal Structure ◽  
High Resolution ◽  
Carbonic Anhydrase ◽  
Quantum Chemical Calculations ◽  
Quantum Chemical ◽  
Computational Analysis ◽  
Structure Modeling ◽  
Carbonic Anhydrases ◽  
Carbonic Anhydrase Inhibitors ◽  
Insight Into

Carborane-based compounds are promising lead structures for development of inhibitors of carbonic anhydrases (CAs). Here, we report structural and computational analysis applicable to structure-based design of carborane compounds with selectivity toward the cancer-specific CAIX isoenzyme. We determined the crystal structure of CAII in complex with 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane at 1.0 Å resolution and used this structure to model the 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane interactions with CAIX. A virtual glycine scan revealed the contributions of individual residues to the energy of binding of 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane to CAII and CAIX, respectively.

scholarly journals Amino Acids as Building Blocks for Carbonic Anhydrase Inhibitors

2018 ◽  
Author(s):  
Niccolò Chiaramonte ◽  
Maria Novella Romanelli ◽  
Elisabetta Teodori ◽  
Claudiu Supuran
Keyword(s):  
Organic Chemistry ◽  
Amino Acids ◽  
Carbonic Anhydrase ◽  
Chemical Properties ◽  
Building Blocks ◽  
Carbonic Anhydrases ◽  
Carbonic Anhydrase Inhibitors ◽  
Physiological Processes ◽  
Long Time ◽  
Reversible Hydration

Carbonic Anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life kingdoms, classified into seven genetically different families (α-θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3-) and protons (H+). Fifteen isoforms of human CA (hCA I-XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or the progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) are used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.

scholarly journals Novel 1,3,5-Triazinyl Aminobenzenesulfonamides Incorporating Aminoalcohol, Aminochalcone and Aminostilbene Structural Motifs as Potent Anti-VRE Agents, and Carbonic Anhydrases I, II, VII, IX, and XII Inhibitors

2021 ◽  
Vol 23 (1) ◽  
pp. 231
Author(s):  
Eva Havránková ◽  
Vladimír Garaj ◽  
Šárka Mascaretti ◽  
Andrea Angeli ◽  
Zuzana Soldánová ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Tumor Cell Line ◽  
Vancomycin Resistant Enterococcus ◽  
Carbonic Anhydrases ◽  
Active Compounds ◽  
Structural Motifs ◽  
Vancomycin Resistant ◽  
Colorectal Tumor Cell ◽  
Molecular Modeling And Docking ◽  
The Brain

A series of 1,3,5-triazinyl aminobenzenesulfonamides substituted by aminoalcohol, aminostilbene, and aminochalcone structural motifs was synthesized as potential human carbonic anhydrase (hCA) inhibitors. The compounds were evaluated on their inhibition of tumor-associated hCA IX and hCA XII, hCA VII isoenzyme present in the brain, and physiologically important hCA I and hCA II. While the test compounds had only a negligible effect on physiologically important isoenzymes, many of the studied compounds significantly affected the hCA IX isoenzyme. Several compounds showed activity against hCA XII; (E)-4-{2-[(4-[(2,3-dihydroxypropyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (31) and (E)-4-{2-[(4-[(4-hydroxyphenyl)amino]-6-[(4-styrylphenyl)amino]-1,3,5-triazin-2-yl)amino]ethyl}benzenesulfonamide (32) were the most effective inhibitors with KIs = 4.4 and 5.9 nM, respectively. In addition, the compounds were tested against vancomycin-resistant Enterococcus faecalis (VRE) isolates. (E)-4-[2-({4-[(4-cinnamoylphenyl)amino]-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2-yl}amino)ethyl]benzenesulfonamide (21) (MIC = 26.33 µM) and derivative 32 (MIC range 13.80–55.20 µM) demonstrated the highest activity against all tested strains. The most active compounds were evaluated for their cytotoxicity against the Human Colorectal Tumor Cell Line (HCT116 p53 +/+). Only 4,4’-[(6-chloro-1,3,5-triazin-2,4-diyl)bis(iminomethylene)]dibenzenesulfonamide (7) and compound 32 demonstrated an IC50 of ca. 6.5 μM; otherwise, the other selected derivatives did not show toxicity at concentrations up to 50 µM. The molecular modeling and docking of active compounds into various hCA isoenzymes, including bacterial carbonic anhydrase, specifically α-CA present in VRE, was performed to try to outline a possible mechanism of selective anti-VRE activity.

scholarly journals Synthesis and Evaluation of New Phthalazine Urea and Thiourea Derivatives as Carbonic Anhydrase Inhibitors

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Nurcan Berber ◽  
Mustafa Arslan ◽  
Emre Yavuz ◽  
Cigdem Bilen ◽  
Nahit Gencer
Keyword(s):  
Carbonic Anhydrase ◽  
Nitro Group ◽  
Zinc Ion ◽  
Inhibitory Effect ◽  
Carbonic Anhydrases ◽  
Coumarin Derivatives ◽  
Inhibitory Effects ◽  
Carbonic Anhydrase Inhibitors ◽  
Thiourea Derivatives ◽  
Amine Derivative

A new series of phthalazine substituted urea and thiourea derivatives were synthesized, and their inhibitory effects on the activity of purified human carbonic anhydrases (hCAs I and II) were evaluated. 2H-Indazolo[2,1-b]phthalazine-trione derivative(1)was prepared with 4-nitrobenzaldehyde, dimedone, and phthalhydrazide in the presence of TFA in DMF, and nitro group was reduced to amine derivative(2)with SnCl2·2H2O. The compound was reacted with isocyanates and isothiocyanates to get the final products(3a–p). The results showed that all the synthesized compounds inhibited the CA isoenzymes activity.3a(IC50= 6.40 µM for hCA I and 6.13 µM for hCA II) has the most inhibitory effect. The synthesized compounds are very bulky to be able to bind near the zinc ion, and they much more probably bind as the coumarin derivatives.

scholarly journals Non-classical β-carbonic anhydrase inhibitors-towards novel anti-mycobacterials

MedChemComm ◽  
2014 ◽  
Vol 5 (10) ◽  
pp. 1563-1566 ◽  
Author(s):  
Natascha von Gnielinski ◽  
Lisa Nienaber ◽  
Lyndel Mason ◽  
Samantha Ellis ◽  
James A. Triccas ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Drug Targets ◽  
Carbonic Anhydrases ◽  
Carbonic Anhydrase Inhibitors ◽  
Essential Protein

Mycobacterial carbonic anhydrases, such as the essential protein Rv3588c, are attractive drug targets since they constitute a different class of carbonic anhydrases than those found in humans.

Inhibition of carbonic anhydrases by a substrate analog: benzyl carbamate directly coordinates the catalytic zinc ion mimicking bicarbonate binding

2018 ◽  
Vol 54 (73) ◽  
pp. 10312-10315 ◽  
Author(s):  
Giuseppina De Simone ◽  
Andrea Angeli ◽  
Murat Bozdag ◽  
Claudiu T. Supuran ◽  
Jean-Yves Winum ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Mode ◽  
Zinc Ion ◽  
Carbonic Anhydrases ◽  
Carbonic Anhydrase Inhibitors ◽  
Lead Compounds ◽  
Substrate Analog ◽  
Catalytic Zinc

N-Unsubstituted carbamates can be used as lead compounds for the development of carbonic anhydrase inhibitors possessing a binding mode similar to bicarbonate.

Carbonic anhydrase inhibitors. Inhibition of the fungal β-carbonic anhydrases from Candida albicans and Cryptococcus neoformans with boronic acids

2009 ◽  
Vol 19 (10) ◽  
pp. 2642-2645 ◽  
Author(s):  
Alessio Innocenti ◽  
Jean-Yves Winum ◽  
Rebecca A. Hall ◽  
Fritz A. Mühlschlegel ◽  
Andrea Scozzafava ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Carbonic Anhydrase ◽  
Cryptococcus Neoformans ◽  
Boronic Acids ◽  
Carbonic Anhydrases ◽  
Carbonic Anhydrase Inhibitors
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