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γ-Class carbonic anhydrases (CAs; EC 184.108.40.206) lack of extended inhibition characterization in comparison to α- and β-class isozymes. For this reason, a panel of 22 phenols was investigated here for the inhibition of the γ-CAs from the pathogenic bacteria Burkholderia pseudomallei (BpsCAγ), Porphyromonas gingivalis (PgiCA), Vibrio cholerae (VchCAγ) and from the antarctic bacteria Pseudoalteromonas haloplanktis (PhaCAγ) and Colwellia psychrerythraea (CpsCAγ). The exploration of the chemical space around the main phenolic group led to the discovery of a number of such derivatives showing effective, sometimes sub-micromolar inhibition against BpsCAγ (Ks 0.45-8.6 µM), PgiCA (Ks 0.36-9.8 µM) and VchCAγ (Ks 0.47-9.6 µM). A subset of compounds even demonstrated a significant selectivity for the target γ-CAs over the human physiologically most relevant isoform CA II. This study enriches the inhibitory profiles database for γ-class CAs and promotes the identification of new potent and selective inhibitors against bacterial isoforms over human off-target ones. These agents are of remarkable interest and importance in the search of novel, worldwide required, antibiotic agents possessing alternative mechanisms of action as a strategy to overcome the spread to antimicrobic resistance.
This article was published in the following journal.
Name: Bioorganic chemistry
Inflammation and vascular smooth muscle cell (VSMC) phenotypic switching are causally linked to pulmonary arterial hypertension (PAH) pathogenesis. Carbonic anhydrase inhibition (CAI) induces mild met...
Sulfonamides represent an important class of drugs because of their inhibitory effect on carbonic anhydrases (CAs). We therefore synthesized several ureidobenzenesulfonamides and evaluated their bCA I...
Carbonic anhydrases (CA, EC 220.127.116.11) are Zinc metalloenzymes and are present throughout most living organisms. Among the catalytically active isoforms are the cytosolic CA I and II, and tumor-associat...
Sixteen 5-aryl-substituted isothiazol-3(2H)-one-1,(1)-(di)oxide analogs have been prepared from the corresponding 5-chloroisothiazol-3(2H)-one-1-oxide or -1,1-dioxide by a Suzuki-Miyaura cross-coupli...
The carbonic anhydrase (CA) inhibitory activity of newly synthesized compounds 4-21 against the human CA (hCA) isoforms I, II, IX, and XII was measured and compared to that of standard sulfonamide inh...
The investigators propose to study the carbonic anhydrase inhibition (acetazolamide) associated with concomitant radiochemotherapy in localized small cell lung cancer due to: 1. The ove...
The purpose of this study is to determine if diabetic retinopathy can be treated with prostaglandin analogues, prostaglandin synthesis inhibitors or carbonic anhydrases inhibitors.
Cyclooxygenase-2 (COX-2) inhibitors have become a common analgesic treatment option for patients with arthritis. However, long-term treatment has been associated with increased cardiovascu...
The study's main objective is to investigate the effects of acute consumption of a preparation containing 100 mg of a specific phenolic compound (patent pending, P201531587) on systolic BP...
An acute, randomized, placebo controlled, double blinded crossover study in health subjects. Participants will complete 4 intervention arms in random order consisting of a placebo control ...
A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES.
A benzene-sulfonamide-furan. It is used as a diuretic that affects the concentrating ability of the KIDNEY, increases SODIUM CHLORIDE excretion, but may not spare POTASSIUM. It inhibits CARBONIC ANHYDRASES and may increase the blood URIC ACID level.
A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of CARBON DIOXIDE from the tissues to the LUNG. EC 18.104.22.168.
One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)
A cytosolic carbonic anhydrase isoenzyme found widely distributed in cells of almost all tissues. Deficiencies of carbonic anhydrase II produce a syndrome characterized by OSTEOPETROSIS, renal tubular acidosis (ACIDOSIS, RENAL TUBULAR) and cerebral calcification. EC 4.2.1.-