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.

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.

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.

Synthesis and biological activity of novel thiourea derivatives as carbonic anhydrase inhibitors

2014 ◽  
Vol 30 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Neslihan Korkmaz ◽  
Oday A. Obaidi ◽  
Murat Senturk ◽  
Demet Astley ◽  
Deniz Ekinci ◽  
...  
Keyword(s):  
Biological Activity ◽  
Carbonic Anhydrase ◽  
Carbonic Anhydrase Inhibitors ◽  
Thiourea Derivatives

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 In vitro inhibition of purified human carbonic anhydrase I and II by novel fluorene derivatives

2014 ◽  
Vol 33 (2) ◽  
pp. 199 ◽  
Author(s):  
Hülya Demirhan ◽  
Mustafa Arslan ◽  
Mustafa Oguzhan Kaya ◽  
Yeşim Kaya ◽  
Nahit Gençer ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Human Erythrocytes ◽  
Affinity Column ◽  
Inhibitory Effects ◽  
Thiourea Derivatives ◽  
Carbonic Anhydrase I ◽  
In Vitro Inhibition ◽  
Human Carbonic Anhydrase ◽  
Sepharose 4B

<p>In this study, 9-benzylidene-9<em>H</em>-fluorene-substituted urea (<strong>5a–p</strong>) and thiourea derivatives <strong>(5q–v)</strong> were synthesized and their inhibitory effects on the activity of human carbonic anhydrase (hCA) I and II were evaluated. hCA I and II were purified from human erythrocytes using a Sepharose 4B-L-tyrosine-sulphanilamide affinity column. All the synthesized compounds inhibited the activity of the hCA I and II isoenzymes. Among the synthesized compounds, <strong>5f</strong><strong> </strong>was found to be the most active (IC<sub>50</sub> = 21.4 μM) for inhibition of hCA I and <strong>5s </strong>was the most active (IC<sub>50</sub> = 25.3 μM) for inhibition of<strong> </strong>hCA II.</p><p><strong><br /></strong></p>

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.

New coumarin derivatives as carbonic anhydrase inhibitors

2013 ◽  
Vol 42 (3) ◽  
pp. 192-198 ◽  
Author(s):  
Mert Olgun Karataş ◽  
Bülent Alici ◽  
Ümit Çakir ◽  
Engin Çetinkaya ◽  
Dudu Demir ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Coumarin Derivatives ◽  
Carbonic Anhydrase Inhibitors

A COMPARATIVE STUDY OF SOME CARBONIC ANHYDRASE INHIBITORS

1961 ◽  
Vol 39 (2) ◽  
pp. 287-295 ◽  
Author(s):  
V. R. Woodford ◽  
Nel Leegwater ◽  
S. M. Drance
Keyword(s):  
Carbon Dioxide ◽  
Intraocular Pressure ◽  
Carbonic Anhydrase ◽  
Comparative Study ◽  
Colorimetric Method ◽  
Inhibitory Effects ◽  
Carbonic Anhydrase Inhibitors ◽  
Gaseous Carbon Dioxide

A modification of a colorimetric method for the determination of carbonic anhydrase is described in which substrate is supplied in the form of gaseous carbon dioxide. Using this method, the inhibitory effects of seven carbonic anhydrase inhibitors used in the control of intraocular pressure were investigated. It was found that equilibrium between enzyme and inhibitor required from 2 minutes to 64 minutes to become established. A comparison of the inhibitory potencies of the various drugs is presented.

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