A5058459755- Enzyme function and inhibition
- Synthesis and Catalytic Reactions
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Reactions and Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Peptidase Inhibition and Analysis
- Synthesis and Biological Evaluation
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Cancer, Hypoxia, and Metabolism
- Chemical Reactions and Isotopes
- Radiopharmaceutical Chemistry and Applications
- Chemical Synthesis and Analysis
- Genomics, phytochemicals, and oxidative stress
- Renin-Angiotensin System Studies
- Protease and Inhibitor Mechanisms
- RNA modifications and cancer
- Peroxisome Proliferator-Activated Receptors
- Congenital heart defects research
- Infant Nutrition and Health
- Metalloenzymes and iron-sulfur proteins
- Neuropeptides and Animal Physiology
- Nanoplatforms for cancer theranostics
- Neuroendocrine Tumor Research Advances
- Enzyme Catalysis and Immobilization
King's College London
2021-2024
University of Antwerp
2019-2024
St Thomas' Hospital
2023-2024
University of Florence
2013-2018
Florence (Netherlands)
2014-2015
Polo d’Innovazione di Genomica
2014-2015
Interuniversity Consortium for Magnetic Resonance
2014
Middle East Technical University
2014
Cyclopropylcarboxylic acids and esters cyclopropylmethanols incorporating bromophenol moieties were investigated as inhibitors of the carbonic anhydrase enzyme (CA; EC 4.2.1.1). The cis- trans-esters 5 6 obtained from reaction 4-allyl-1,2-dimethoxybenzene (4) with ethyl diazoacetate, which after bromination Br2 gave two isomeric monobromides (11 15), four dibromides (12, 13, 16, 17), tribromides (14 18). carboxylic 7, 8, 19–26 thereafter by hydrolysis synthesized esters. All these...
6-Substituted sulfocoumarins bearing the carboxamido, trimethylammonium as well cyano and methoxy moieties with interesting inhibitory activity/selectivity against tumor associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX XII are reported. Moieties leading to best inhibition were tert-butylcarboxamido, phenylcarboxamido, 4-pyridylcarboxamido, KI values of 2.1–8.1 nM. No off-target II I was observed. A number these compounds evaluated HT-29 colon cancer cell lines ex vivo....
The X-ray co-crystallization experiments of saccharin derivative with carbonic anhydrase revealed hydrolysis isothiazole ring and guided design new inhibitors.
Abstract The reaction mechanism of the carbonic anhydrase‐mediated hydrolysis sulfocoumarins to sulfonic acids has been investigated on an enzyme cluster model using B3LYP hybrid density functional theory (DFT) and QST procedure for Transition State (TS) search. A multistep process was highlighted, with rate‐determining step identified in initial dual nucleophilic/acidic attack zinc‐bound hydroxide ion sulfocoumarin sulfur atom C3=C4 double bond. reported multi‐step process, combined SAR...
Mouse models are invaluable tools for radiotracer development and validation. They are, however, expensive, low throughput, constrained by animal welfare considerations. Here, we assessed the chicken chorioallantoic membrane (CAM) as an alternative to mice preclinical cancer imaging studies. NCI-H460 FLuc cells grown in Matrigel on CAM formed vascularized tumors of reproducible size without compromising embryo viability. By designing a simple method vessel cannulation it was possible perform...
The α-carbonic anhydrases (CAs, EC 4.2.1.1) show catalytic versatility acting as esterases with carboxylic, sulfonic, and phosphate esters. Here we prove by kinetic, spectroscopic, MS studies that they also possess thioesterase activity a dithiocarbamate ester substrate (PhSO2NHCSSMe). Its CA-mediated hydrolysis leads to benzenesulfonamide, methyl mercaptan, COS. CA may be useful for designing prodrug enzyme inhibitors, whereas some isoforms use this modulating physiologic/pathologic...
Carbonic anhydrases (CAs) are ubiquitous Zn metallo-enzymes that catalyze the reversible hydration/dehydration of CO2/HCO3(-). CAs involved in many key biological processes, therefore their inhibition has become an attractive research field. Distinct families CA inhibitors (CAIs) have been reported, most them interacting with Zn(II) at active site. Some compounds such as coumarins hydrolyzed before binding entrance site cavity, and thus behave "suicide" inhibitors. This study reports first...
Mannich bases of thymol were synthesized. The aminomethylation reaction was realised in the ortho position phenol for compounds 2 (dipropylamine), 3 (benzylamine), and 4 (dibenzylamine) while it from para 1 (dimethylamine), 5 (piperidine), 6 (morpholine) 7 (N-methylpiperazine). carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects asssessed against hCA I II. All moderately inhibited cytotoxicity four human oral squamous cell carcinoma lines compared those three normal cells. Tumor...
Phenolic mono Mannich bases [2-[4-hydroxy-3-(aminomethyl)benzylidene]-2,3-dihydro-1H-inden-1-one (8-15)] and bis [2-[4-hydroxy-3,5-bis(aminomethyl)benzylidene]-2, 3-dihydro-1H-inden-1-one (2-7)] were synthesized starting from 2-(4-hydroxybenzylidene)-2, 3-dihydro-inden-1-one (1). This study was designed in order to investigate the carbonic anhydrase (CA, EC 4.2.1.1) inhibitory properties of a library compounds incorporating phenol functional group. All prepared showed low inhibition...
A series of 6-substituted 2-benzoxathiine-2,2-dioxides were synthesized starting from 2,5-dihydroxybenzaldehyde, and then screened in vitro for their inhibition properties against five human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms. All the compounds showed excellent selectivity mitochondrial (hCA VA) tumor associated IX XII) enzymes.
A series of substituted pyrrolidines and piperidines were synthesized using superacid HF/SbF5 chemistry. Investigated as inhibitors several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, i.e. the cytosolic hCA I II well tumor-associated transmembrane isoforms IX XII, these compounds showed a never yet reported selectivity toward II. In tertiary benzenesulfonamide family, this class points out new mechanism action for inhibition.
A series of ureido and bis-ureido derivatives were prepared by reacting histamine with alkyl/aryl-isocyanates or di-isocyanates. The obtained assayed as activators the enzyme carbonic anhydrase (CA, EC 4.2.1.1), due to fact that itself has this biological activity. Although inhibition CAs pharmacological applications in field antiglaucoma, anticonvulsant, anticancer, anti-infective agents, activation these enzymes is not yet properly exploited pharmacologically for cognitive enhancement...
N-substituted maleimides were synthesized from maleic anhydride and primary amines. 1,4-Dibromo-dibenzo[e,h]bicyclo-[2,2,2]octane-2,3-dicarboximide derivatives (4a-f) prepared by the [4+2] cycloaddition reaction of dibromoanthracenes with maleimide derivatives. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects new assayed against human (h) isozymes hCA I, II, IX, XII. All tested bicyclo dicarboximide exhibited excellent in nanomolar range, Ki values range 117.73-232.87 nM I...
Fibroblast activation protein (FAP) is a very reliable biomarker for tissue remodeling. FAP has so far mainly been studied in oncology, but there growing interest the enzyme other diseases like fibrosis. Recently, FAP-targeting diagnostics and therapeutics have emerged, of which so-called FAPIs are among most promising representatives. typically relatively high molecular weight contain polar, multicharged chelator moieties. While this not limiting application more druglike could be required...
N-Protected amino acids (Gly, Ala and Phe) were reacted with substituted coumarin quinolinone derivatives, leading to the corresponding N-protected acid-coumarin/quinolinone conjugates. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of new compounds was assessed against various human (h) isoforms, such as hCA I, II, IV XII. conjugates inactive enzyme inhibitors, whereas coumarins ineffective I/II inhibitors (KIs > 50 μM) but submicromolar XII inhibition constants ranging between...