A5035013697- Enzyme function and inhibition
- Synthesis and Catalytic Reactions
- Cholinesterase and Neurodegenerative Diseases
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Reactions and Mechanisms
- Synthesis and Biological Evaluation
- Cancer, Hypoxia, and Metabolism
- Nitric Oxide and Endothelin Effects
- Metal complexes synthesis and properties
- Polyamine Metabolism and Applications
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Synthesis and biological activity
- Chemical Synthesis and Analysis
- Electrochemical sensors and biosensors
- Chemical Reaction Mechanisms
- Computational Drug Discovery Methods
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Crystallization and Solubility Studies
- Adenosine and Purinergic Signaling
- X-ray Diffraction in Crystallography
- Chemical synthesis and alkaloids
- Synthesis and Characterization of Heterocyclic Compounds
- Ion channel regulation and function
- Enzyme Catalysis and Immobilization
University of Florence
2016-2025
Universidade Federal do Rio de Janeiro
2017-2022
Agricultural Biotechnology Institute
2022
Biocat
2022
Bioinova (Czechia)
2022
Virginia–Maryland College of Veterinary Medicine
2022
Virginia Tech
2022
Maulana Azad National Urdu University
2022
Florence (Netherlands)
2010-2021
Institute of Biosciences and Bioresources
2015-2021
Abstract Carbonic anhydrase IX (CAIX) is a hypoxia and HIF-1–inducible protein that regulates intra- extracellular pH under hypoxic conditions promotes tumor cell survival invasion in microenvironments. Interrogation of 3,630 human breast cancers provided definitive evidence CAIX as an independent poor prognostic biomarker for distant metastases survival. shRNA-mediated depletion expression 4T1 mouse metastatic cancer cells capable inducing resulted regression orthotopic mammary tumors...
Acidic extracellular pH (pHe) is a typical attribute of tumor microenviroment, which has an impact on cancer development and treatment outcome. It was believed to result from accumulation lactic acid excessively produced by glycolysis. However, metabolic profiles glycolysis‐impaired tumors have revealed that CO 2 significant source acidity, thereby indicating contribution carbonic anhydrase (CA). The tumor‐associated CA IX isoform the best candidate, because its enzyme domain highly active,...
Carbonic anhydrases (CAs, EC 4.2.1.1) are wide-spread zinc enzymes, present in archaeo- and eubacteria, algae, green plants animals. Within these organisms CAs encoded by three distinct, evolutionarily unrelated gene families: the α-CA, β-CA γ-CA families, respectively. These enzymes very efficient catalysts for reversible hydration of CO2 to bicarbonate; α-CAs possess high versatility, being able catalyse other hydrolytic processes. It is not known whether reactions catalysed (than...
The X-ray crystal structure of the adduct between zinc metalloenzyme carbonic anhydrase II (CA, EC 4.2.1.1) with recently discovered natural product coumarin derivative 6-(1S-hydroxy-3-methylbutyl)-7-methoxy-2H-chromen-2-one showed hydrolysis product, a cis-2-hydroxy-cinnamic acid derivative, and not parent coumarin, bound within enzyme active site. inhibitor exhibits an extended, two-arm conformation that effectively plugs entrance to site no interactions catalytically crucial ion. is...
Carbonic anhydrase (CA) IX is a plasma membrane-associated member of the α-CA enzyme family, which involved in solid tumor acidification. It marker hypoxia and prognostic factor several human cancers. An aberrant increase CA expression chronic during development various carcinomas contributes to tumorigenesis through at least two mechanisms: pH regulation cell adhesion control. Here we report X-ray structure catalytic domain complex with classical, clinically used sulfonamide inhibitor,...
A series of ureido-substituted benzenesulfonamides was prepared that showed a very interesting profile for the inhibition several human carbonic anhydrases (hCAs, EC 4.2.1.1), such as hCAs I and II (cytosolic isoforms) IX XII (transmembrane, tumor-associated enzymes). Excellent all these isoforms has been observed with various members series, depending on substitution pattern urea moiety. Several low nanomolar CA IX/XII inhibitors also showing good selectivity transmembrane over cytosolic...
By optimizing binding to a selected target protein, modern drug research strives develop safe and efficacious agents for the treatment of disease. Selective action is intended minimize undesirable side effects from scatter pharmacology. Celecoxib (Celebrex), valdecoxib (Bextra), rofecoxib (Vioxx) are nonsteroidal antiinflammatory drugs (NSAIDs) due selective inhibition inducible cyclooxygenase COX-2 while sparing constitutive COX-1. While contains methyl sulfone constituent, celecoxib...
Coumarin derivatives were recently shown to constitute a totally new class of inhibitors the zinc metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), being hydrolyzed within CA active site 2-hydroxycinnamic acids. We explore here series variously substituted coumarins and thiocoumarin for their interaction with 13 mammalian isoforms, detecting low nanomolar isoform selective inhibitors. The mechanism action this is delineated in detail by resolving X-ray crystal structure II complex...