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 Amino Acids as Building Blocks for Carbonic Anhydrase Inhibitors

Metabolites ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. 36 ◽  
Author(s):  
Niccolò Chiaramonte ◽  
Maria Romanelli ◽  
Elisabetta Teodori ◽  
Claudiu Supuran
Keyword(s):  
Amino Acids ◽  
Carbonic Anhydrase ◽  
Building Blocks ◽  
Carbonic Anhydrase Inhibitors

scholarly journals Effect of Sulfonamides and Their Structurally Related Derivatives on the Activity of ι-Carbonic Anhydrase from Burkholderia territorii

2021 ◽  
Vol 22 (2) ◽  
pp. 571
Author(s):  
Viviana De Luca ◽  
Andrea Petreni ◽  
Alessio Nocentini ◽  
Andrea Scaloni ◽  
Claudiu T. Supuran ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Selective Inhibition ◽  
Extensive Study ◽  
Protein Isoforms ◽  
Carbonic Anhydrases ◽  
Physiological Processes ◽  
Microbial Survival ◽  
Reversible Hydration

Carbonic anhydrases (CAs) are essential metalloenzymes in nature, catalyzing the carbon dioxide reversible hydration into bicarbonate and proton. In humans, breathing and many other critical physiological processes depend on this enzymatic activity. The CA superfamily function and inhibition in pathogenic bacteria has recently been the object of significant advances, being demonstrated to affect microbial survival/virulence. Targeting bacterial CAs may thus be a valid alternative to expand the pharmacological arsenal against the emergence of widespread antibiotic resistance. Here, we report an extensive study on the inhibition profile of the recently discovered ι-CA class present in some bacteria, including Burkholderia territorii, namely BteCAι, using substituted benzene-sulfonamides and clinically licensed sulfonamide-, sulfamate- and sulfamide-type drugs. The BteCAι inhibition profile showed: (i) several benzene-sulfonamides with an inhibition constant lower than 100 nM; (ii) a different behavior with respect to other α, β and γ-CAs; (iii) clinically used drugs having a micromolar affinity. This prototype study contributes to the initial recognition of compounds which efficiently and selectively inhibit a bacterial member of the ι-CA class, for which such a selective inhibition with respect to other protein isoforms present in the host is highly desired and may contribute to the development of novel antimicrobials.

scholarly journals Synthesis, Characterization and Evaluation of Peptide Nanostructures for Biomedical Applications

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4587
Author(s):  
Fanny d’Orlyé ◽  
Laura Trapiella-Alfonso ◽  
Camille Lescot ◽  
Marie Pinvidic ◽  
Bich-Thuy Doan ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biomedical Applications ◽  
Chemical Reactivity ◽  
Physical Stability ◽  
Chemical Properties ◽  
Building Blocks ◽  
Imaging Probes ◽  
Therapeutic Molecules

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.

Carbonic anhydrase activators: Activation of the archaeal β-class (Cab) and γ-class (Cam) carbonic anhydrases with amino acids and amines

2008 ◽  
Vol 18 (23) ◽  
pp. 6194-6198 ◽  
Author(s):  
Alessio Innocenti ◽  
Sabrina A. Zimmerman ◽  
Andrea Scozzafava ◽  
James G. Ferry ◽  
Claudiu T. Supuran
Keyword(s):  
Amino Acids ◽  
Carbonic Anhydrase ◽  
Carbonic Anhydrases

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.

Unconventional amino acids in medicinal chemistry: First report on taurine merged within carbonic anhydrase inhibitors

2020 ◽  
Vol 103 ◽  
pp. 104236 ◽  
Author(s):  
Özlem Akgül ◽  
Andrea Angeli ◽  
Daniela Vullo ◽  
Fabrizio Carta ◽  
Claudiu T. Supuran
Keyword(s):  
Amino Acids ◽  
Carbonic Anhydrase ◽  
Medicinal Chemistry ◽  
Carbonic Anhydrase Inhibitors ◽  
First Report

scholarly journals THE INCREASED OF CARBONIC ANHYDRASE IN LIVER TISSUE OF RAT INDUCED BY CHRONIC SYSTEMIC HYPOXIA

2018 ◽  
Vol 1 (1) ◽  
pp. 1-6
Author(s):  
Rahmawati Ridwan ◽  
Febriana Catur Iswanti ◽  
Mohamad Sadikin
Keyword(s):  
Oxidative Stress ◽  
Liver Tissue ◽  
Specific Activity ◽  
Hypoxic Condition ◽  
Carbonic Anhydrases ◽  
Acid Base Balance ◽  
Physiological Processes ◽  
Systemic Hypoxia ◽  
Base Balance ◽  
Reversible Hydration

Background: Carbonic anhydrases (CAs) are metalloenzymes which catalyze the reversible hydration/dehydration reaction of CO2, in order to maintain the cell homeostasis. These enzymes are found in various tissues and involve in a number of different physiological processes, including ion transport, acid-base balance, bone formation, gluconeogenesis and so on.Objective: To examine the specific activity of CA and to observe the liver tissue respond to oxidative stress by measured the malondialdehyde (MDA) concentration, in rat liver tissue induced by chronic systemic hypoxia for 1, 3, 5, 7 and 14 days of hypoxia.Results: The study showed that the activity of CA which induced by chronic systemic hypoxia significantly increasing at early exposure to the hypoxic condition, at day 1 and days 3 of hypoxia (0.281 and 0.262 nmol/mg protein/minute compared to control 0.155 nmol/mg protein/minute) (p<0.05). No statistically difference at treatments of hypoxia  5, 7 and 14 days. The concentration of MDA also increased significantly in day 3 of liver tissue hypoxia (0.013 nmol/mg compared to control 0.009 nmol/mg liver tissue) (p<0.05), and no statistically differences at day 1, 5, 7, and 14 days of hypoxia.Conclusion : There was damage of membrane cells affected by oxidative stress in liver tissue of rat induced by chronic systemic hypoxia.

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.

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