A5027722233- Enzyme function and inhibition
- Synthesis and Catalytic Reactions
- Chemical Reactions and Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Phenothiazines and Benzothiazines Synthesis and Activities
- Particle Dynamics in Fluid Flows
- Nitric Oxide and Endothelin Effects
- Chemical Reaction Mechanisms
- Fluid Dynamics and Turbulent Flows
- Electrochemical sensors and biosensors
- Fluid Dynamics and Mixing
- Granular flow and fluidized beds
- Crystallization and Solubility Studies
- Peptidase Inhibition and Analysis
- Polyamine Metabolism and Applications
- Click Chemistry and Applications
- X-ray Diffraction in Crystallography
- Biochemical and Molecular Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Metal-Catalyzed Oxygenation Mechanisms
- Chemical synthesis and alkaloids
- Synthesis and Characterization of Heterocyclic Compounds
- Ocean Waves and Remote Sensing
- Tropical and Extratropical Cyclones Research
- Fluid Dynamics and Heat Transfer
Sapienza University of Rome
2025
Institut Jean Le Rond d'Alembert
2016-2021
Centre National de la Recherche Scientifique
2016-2021
Iowa State University
2021
Bissell (United States)
2021
Sorbonne Université
2016-2021
University of Pisa
2016-2019
University of Florence
2006-2017
Institut des Biomolécules Max Mousseron
2011
University of Gdańsk
2010
Carbonic anhydrase IX (CA IX) is an exceptional member of the CA protein family; in addition to its classical role pH regulation, it has also been proposed participate cell proliferation, adhesion, and tumorigenic processes. To characterize biochemical properties this membrane protein, two soluble recombinant forms were produced using baculovirus-insect expression system. The proteins consisted either catalytic domain only form) or extracellular domain, which included both proteoglycan...
Carbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, phenols, and coumarins. Polyamines such as spermine, spermidine, many synthetic congeners described to constitute a novel class of CA inhibitors (CAIs), interacting with the different isozymes efficiency from low nanomolar millimolar range. The main structure−activity relationship for these CAIs have been delineated: length molecule, number amine moieties, their functionalization parameters controlling activity. X-ray...
A lately discovered carbonic anhydrase (hCA, EC 4.2.1.1), the mitochondrial hCA VB, was cloned, expressed, and purified. Kinetic parameters proved it to be 3.37 times more effective than VA as a catalyst for physiological reaction, with kcat = 9.5 × 105 s-1 kcat/KM 9.8 107 M-1 s-1, being second only II among 16 isoforms presently known in humans. We investigated inhibition of VB library sulfonamides/sulfamates, some which are clinically used compounds. Benzenesulfonamides were ineffective...
We report the synthesis of a series benzene sulfonamides containing triazole-O-glycoside tails for evaluation as carbonic anhydrase (CA) inhibitors. These glycoconjugates were synthesized by 1,3-dipolar cycloaddition reaction 4-azidobenzenesulfonamide with O-propynyl glycosides. Compounds assessed their ability to inhibit enzymatic activity physiologically dominant isozymes hCA I and II tumor-associated isozyme IX (h = human). Against these compounds either micromolar or low-nanomolar...
A matter of taste: The sweetner saccharin (a cyclic sulfimide, see picture) is nearly completely absorbed and eliminated through the urine, thus exposed to many different proteins in body. It binds at nanomolar levels some carbonic anhydrases this provokes question its inert properties. known that plasma level slowly decreases after oral dosing, CAVI binding could explain unpleasant metallic aftertaste. Saccharin oldest artificial sweetener, was discovered by serendipity 1879 Fahlberg...
Aryl and heteroaryl sulfonamides (ArSO(2)NH(2)) are therapeutically used to inhibit the catalytic activity of carbonic anhydrases (CAs). Using a "click-tail" approach novel class glycoconjugate benzene have been synthesized that contain diverse carbohydrate-triazole tails. These compounds were assessed for their ability three human CA isozymes in vitro: cytosolic hCA I II transmembrane, tumor-associated IX. This isozyme has minimal expression normal tissue but is overexpressed hypoxic tumors...
The Root effect is a pH-dependent reduction in hemoglobin-O2 carrying capacity. Specific to ray-finned fishes, the has been ascribed specialized roles retinal oxygenation and swimbladder inflation. We report that when rainbow trout are exposed elevated water carbon dioxide (CO2), red muscle partial pressure of oxygen (PO2) increases by 65%--evidence hemoglobins enhance general tissue O2 delivery during acidotic stress. Inhibiting carbonic anhydrase (CA) plasma abolished this effect. argue CA...
Coumarins constitute a general and totally new class of inhibitors the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), binding at entrance active site cavity. We report here that coumarin-binding in CAs may interact with diverse compounds, such as antiepileptic drug lacosamide, which inhibits mammalian I−XV, inhibition constants range 331 nM to 4.56 μM. Its X-ray crystal structure adduct CA II reveals molecular basis for this inhibition. Lacosamide was found site, making favorable van der...
Enhanced receptor selectivity: Carbonic anhydrase inhibitors are relevant for both cancer diagnosis and therapy. Combining non-radioactive Re compounds with their radioactive 99mTc homologs enables the use of identical molecules therapy imaging (theragnostic). The syntheses in vitro evaluation [(Cp-R)M(CO)3] (Cp=cyclopentadienyl, M=Re, 99mTc) R being a highly potent carbonic-anhydrase-targeting vector is reported (see picture).
The sulfamide analogue of the antiepileptic drug topiramate is a 210 times less potent inhibitor isozyme II zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) compared to but effectively inhibits isozymes CA VA, VB, VII, XIII, and XIV (KI in range 21−35 nM). Its weak binding due clash between one methyl group Ala65 may be exploited for design compounds with lower affinity this ubiquitous isozyme, as unique II. As shown by X-ray crystallography, binds deprotonated moiety coordinated Zn(II)...
The Rv3273 gene product of Mycobacterium tuberculosis, a β-carbonic anhydrase (CA, EC 4.2.1.1), mtCA 3, shows appreciable catalytic activity for CO2 hydration (kcat 4.3 × 105 s−1, and kcat/Km 4.0 107 M−1·s−1). A series sulfonamides/sulfamates was assayed their interaction with 3. Sulfanilyl-sulfonamides, acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, zonisamide, showed effective, submicromolar inhibition (KIs 104−611 nM), the best...
In order to discover novel probes that may help in the investigation and control of infectious diseases through a new mechanism action, we have evaluated library phenol-based natural products (NPs) for enzyme inhibition against four recently characterized pathogen β-family carbonic anhydrases (CAs). These include CAs from Mycobacterium tuberculosis, Candida albicans, Cryptococcus neoformans as well α-family human CA I II comparison. Many NPs selectively inhibited mycobacterial fungal β-CAs,...
The process of drug discovery and development is time-consuming costly, the probability success low. Therefore, there rising interest in repositioning existing drugs for new medical indications. When successful, this reduces risk failure costs associated with de novo development. However, many cases, indications have been found serendipitously. Thus a clear need establishment rational methods repositioning.In study, we established database call "PharmDB" which integrates data disease...