Mycobacterial carbonic anhydrase inhibition with phenolic acids and esters: kinetic and computational investigations

2016 ◽  
Vol 14 (35) ◽  
pp. 8322-8330 ◽  
Author(s):  
Ylenia Cau ◽  
Mattia Mori ◽  
Claudiu T. Supuran ◽  
Maurizio Botta
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Carbonic Anhydrase ◽  
Phenolic Acids ◽  
Specific Inhibition ◽  
Carbonic Anhydrases ◽  
Carbonic Anhydrase Inhibition

Phenolic acids and their ester derivatives show specific inhibition of beta-carbonic anhydrases from Mycobacterium tuberculosis, and are interesting anti-mycobacterial leads.

Exploring carbonic anhydrase inhibition with multimeric coumarins displayed on a fullerene scaffold

2015 ◽  
Vol 13 (27) ◽  
pp. 7445-7451 ◽  
Author(s):  
Marta Abellán-Flos ◽  
Muhammet Tanç ◽  
Claudiu T. Supuran ◽  
Stéphane P. Vincent
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrases ◽  
Carbonic Anhydrase Inhibition ◽  
Suicide Inhibitors

This study reports the first synthesis of multimeric suicide inhibitors of carbonic anhydrases.

Discovery of potent nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) inhibitors with ancillary carbonic anhydrase inhibition for cancer (immuno)therapy

2021 ◽  
Author(s):  
Sang-Yong Lee ◽  
Vigneshwaran Namasivayam ◽  
Nader M. Boshta ◽  
Arianna Perotti ◽  
Salahuddin Mirza ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Carbonic Anhydrases ◽  
Nucleotide Pyrophosphatase ◽  
Carbonic Anhydrase Inhibition

The first potent NPP3 inhibitors were discovered, which were found to additionally block cancer-related carbonic anhydrases.

scholarly journals Evaluation of Thio- and Seleno-Acetamides Bearing Benzenesulfonamide as Inhibitor of Carbonic Anhydrases from Different Pathogenic Bacteria

2020 ◽  
Vol 21 (2) ◽  
pp. 598 ◽  
Author(s):  
Andrea Angeli ◽  
Mariana Pinteala ◽  
Stelian S. Maier ◽  
Bogdan C. Simionescu ◽  
Andrea Milaneschi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Carbonic Anhydrase ◽  
Burkholderia Pseudomallei ◽  
Pathogenic Bacteria ◽  
Antibacterial Agents ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Physiological Role ◽  
Carbonic Anhydrases ◽  
Serovar Typhimurium ◽  
Isoform Selectivity

A series of 2-thio- and 2-seleno-acetamides bearing the benzenesulfonamide moiety were evaluated as Carbonic Anhydrase (CA, EC 4.2.1.1) inhibitors against different pathogenic bacteria such as the Vibrio cholerae (VchCA-α and VchCA-β), Burkholderia pseudomallei (BpsCA-β and BpsCA-γ), Mycobacterium tuberculosis (Rv3723-β) and the Salmonella enterica serovar Typhimurium (StCA2-β). The molecules represent interesting leads worth developing as innovative antibacterial agents since they possess new mechanism of action and isoform selectivity preferentially against the bacterial expressed CAs. The identification of potent and selective inhibitors of bacterial CAs may lead to tools also useful for deciphering the physiological role(s) of such proteins.

scholarly journals Carbonic anhydrase inhibitors modify intracellular pH transients and contractions of rat middle cerebral arteries during CO2/HCO3– fluctuations

2017 ◽  
Vol 38 (3) ◽  
pp. 492-505 ◽  
Author(s):  
Jacob K Rasmussen ◽  
Ebbe Boedtkjer
Keyword(s):  
Carbonic Anhydrase ◽  
Intracellular Ph ◽  
Cerebral Arteries ◽  
Carbonic Anhydrase Activity ◽  
Carbonic Anhydrases ◽  
Intracellular Acidification ◽  
Acid Base ◽  
Surface Ph ◽  
Middle Cerebral Arteries ◽  
Carbonic Anhydrase Inhibition

The CO2/HCO3– buffer minimizes pH changes in response to acid–base loads, HCO3– provides substrate for Na+,HCO3–-cotransporters and Cl–/HCO3–-exchangers, and H+ and HCO3– modify vasomotor responses during acid–base disturbances. We show here that rat middle cerebral arteries express cytosolic, mitochondrial, extracellular, and secreted carbonic anhydrase isoforms that catalyze equilibration of the CO2/HCO3– buffer. Switching from CO2/HCO3–-free to CO2/HCO3–-containing extracellular solution results in initial intracellular acidification due to hydration of CO2 followed by gradual alkalinization due to cellular HCO3– uptake. Carbonic anhydrase inhibition decelerates the initial acidification and attenuates the associated transient vasoconstriction without affecting intracellular pH or artery tone at steady-state. Na+,HCO3–-cotransport and Na+/H+-exchange activity after NH4+-prepulse-induced intracellular acidification are unaffected by carbonic anhydrase inhibition. Extracellular surface pH transients induced by transmembrane NH3 flux are evident under CO2/HCO3–-free conditions but absent when the buffer capacity and apparent H+ mobility increase in the presence of CO2/HCO3– even after the inhibition of carbonic anhydrases. We conclude that (a) intracellular carbonic anhydrase activity accentuates pH transients and vasoconstriction in response to acute elevations of pCO2, (b) CO2/HCO3– minimizes extracellular surface pH transients without requiring carbonic anhydrase activity, and (c) carbonic anhydrases are not rate limiting for acid–base transport across cell membranes during recovery from intracellular acidification.

Are Carbonic Anhydrases Suitable Targets to Fight Protozoan Parasitic Diseases?

2019 ◽  
Vol 25 (39) ◽  
pp. 5266-5278 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Claudiu T. Supuran ◽  
Giuseppina De Simone
Keyword(s):  
Drug Resistance ◽  
Animal Models ◽  
Carbonic Anhydrase ◽  
Drug Target ◽  
Treatment Options ◽  
Parasitic Diseases ◽  
Carbonic Anhydrases ◽  
Extensive Drug Resistance ◽  
Protozoan Infections

Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme Carbonic Anhydrase (CA, EC 4.2.1.1) was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T. cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also effective in cell cultures and animal models of protozoan infections, making them of considerable interest for the development of new antiprotozoan drugs with a novel mechanism of action.

Coumaronochromone as antibacterial and carbonic anhydrase inhibitors from Aerva persica (Burm.f.) Merr.: experimental and first-principles approaches

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Muhammad Imran ◽  
Ahmad Irfan ◽  
Mohammed A. Assiri ◽  
Sajjad H. Sumrra ◽  
Muhammad Saleem ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
First Principles ◽  
Molecular Electrostatic Potential ◽  
Chemical Constituents ◽  
Bacterial Strains ◽  
Hirshfeld Analysis ◽  
Carbonic Anhydrase Inhibition ◽  
Inhibition Studies ◽  
Lowest Unoccupied Molecular Orbitals

AbstractThe Aerva plants are exceptionally rich in phytochemicals and possess therapeutics potential. Phytochemical screening shows that Aerva persica (Burm.f.) Merr. contains highest contents i.e., total phenolics, flavonoids, flavonols, tannins, alkaloids, carbohydrates, anthraquinones and glycosides. In-vitro antibacterial and enzymatic (carbonic anhydrase) inhibition studies on methanol extracts of A. persica indicated the presence of biological active constituents within chloroform soluble portions. Investigation in the pure constituents on the chloroform portions of A. persica accomplished by column chromatography, NMR and MS analysis. The bioguided isolation yields four chemical constituents of coumaronochromone family, namely aervin (1-4). These pure chemical entities (1-4) showed significant antibacterial activity in the range of 60.05–79.21 µg/ml against various bacterial strains using ampicillin and ciprofloxacin as standard drugs. The compounds 1-4 showed promising carbonic anhydrase inhibition with IC50 values of 19.01, 18.24, 18.65 and 12.92 µM, respectively, using standard inhibitor acetazolamide. First-principles calculations revealed comprehensive intramolecular charge transfer in the studied compounds 1-4. The spatial distribution of highest occupied and lowest unoccupied molecular orbitals, ionization potential, molecular electrostatic potential and Hirshfeld analysis revealed that these coumaronochromone compounds would be proficient biological active compounds. These pure constituents may be used as a new pharmacophore to treat leaukomia, epilepsy, glaucoma and cystic fibrosis.

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