Advertisement

Topics

Pyrrolidinone-bearing methylated and halogenated benzenesulfonamides as inhibitors of carbonic anhydrases.

07:00 EST 6th December 2018 | BioPortfolio

Summary of "Pyrrolidinone-bearing methylated and halogenated benzenesulfonamides as inhibitors of carbonic anhydrases."

Two series of benzenesulfonamides bearing methyl groups at ortho/ortho or meta/ortho positions and a pyrrolidinone moiety at para position were synthesized and tested as inhibitors of the twelve catalytically active human carbonic anhydrase (CA) isoforms. Observed binding affinities were determined by fluorescent thermal shift assay and intrinsic binding affinities representing the binding of benzenesulfonamide anion to the Zn(II)-bound water form of CA were calculated. Introduction of dimethyl groups into benzenesulfonamide ring decreased the binding affinity to almost all CA isoforms, but gained in selectivity towards one CA isoform. A chloro group at the meta position of 2,6-dimethylbenzenesulfonamide derivatives did not influence the binding to CA I, but it increased the affinity to all other CAs, especially, CA VII and CA XIII (up to 500 fold). The compounds may be used for further development of CA inhibitors with higher selectivity to particular CA isoforms.

Affiliation

Journal Details

This article was published in the following journal.

Name: Bioorganic & medicinal chemistry
ISSN: 1464-3391
Pages:

Links

DeepDyve research library

PubMed Articles [4701 Associated PubMed Articles listed on BioPortfolio]

Benzenesulfonamides incorporating nitrogenous bases show effective inhibition of β-carbonic anhydrases from the pathogenic fungi Cryptococcus neoformans, Candida glabrata and Malassezia globosa.

There is an urgent need for new chemotherapic agents to treat human fungal infections due to emerging and spreading globally resistance mechanisms. Among the new targets that have been recently invest...

Click-tailed benzenesulfonamides as potent bacterial carbonic anhydrase inhibitors for targeting Mycobacterium tuberculosis and Vibrio cholerae.

A series of 1,2,3-triazole-bearing benzenesulfonamides was assessed for the inhibition of carbonic anhydrases (CA, EC 4.2.1.1) from bacteria Vibrio cholerae (VchCAα and VchCAβ) and Mycobacterium tub...

Design, synthesis and biological evaluation of novel ureido benzenesulfonamides incorporating 1,3,5-triazine moieties as potent carbonic anhydrase IX inhibitors.

A series of novel ureido benzenesulfonamides incorporating 1,3,5-triazine moieties were obtained by reacting 4-isocyanato-benzenesulfonamide (2) with 2-amino-4,6-dicholoro-1,3,5-triazine (4). The 4-(3...

Design, synthesis, and carbonic anhydrase inhibition activity of benzenesulfonamide-linked novel pyrazoline derivatives.

Carbonic anhydrases (CA, EC 4.2.1.1) 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...

Syntesis of thio- and seleno-acetamides bearing benzenesulfonamide as potent inhibitors of human carbonic anhydrase II and XII.

A novel series of thio- and seleno-acetamides bearing benzenesulfonamide were synthetized and tested as human carbonic anhydrase inhibitors. These compounds were tested for the inhibition of four huma...

Clinical Trials [1588 Associated Clinical Trials listed on BioPortfolio]

Pharmacological Intervention in Diabetic Retinopathy

The purpose of this study is to determine if diabetic retinopathy can be treated with prostaglandin analogues, prostaglandin synthesis inhibitors or carbonic anhydrases inhibitors.

Inhibition of CArbonic Anhydrase in Combination With Platinum and Etoposide-based Radiochemotherapy in Patients With Localized Small Cell Lung Cancer

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...

Effects of Dual Cyclooxygenase-2 and Carbonic Anhydrase Inhibition

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...

Fixed Bearing Versus Mobile Bearing Patient Satisfaction and Clinical Outcome Study

The purpose of this study is to determine if there is a patient satisfaction preference of Fixed Bearing versus Mobile Bearing Unicompartmental Knee Arthroplasty (UKA) in patients who are ...

Early Weight Bearing for Unstable Ankle Fractures Undergoing Operative Stabilization

The purpose of this randomized, controlled trial is to estimate the safety of early weight bearing on post ankle surgery. Patients who are indicated to have surgery for unstable ankle fra...

Medical and Biotech [MESH] Definitions

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 4.2.1.1.

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.-

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topic

Assays
An assay is an analytic procedure for qualitatively assessing or quantitatively measuring the presence or amount or the functional activity of a target entity.  This can be a drug or biochemical substance or a cell in an organism or organic sample. ...


Searches Linking to this Article