A5106509821- Enzyme function and inhibition
- Synthesis and Catalytic Reactions
- Chemical Reactions and Mechanisms
- Phenothiazines and Benzothiazines Synthesis and Activities
- Cholinesterase and Neurodegenerative Diseases
- Chemical Synthesis and Analysis
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Synthesis and Biological Evaluation
- Peptidase Inhibition and Analysis
- Educational Games and Gamification
- Click Chemistry and Applications
- Cancer, Hypoxia, and Metabolism
- Chemical Synthesis and Reactions
- Synthesis and biological activity
- Sulfur-Based Synthesis Techniques
- Nanoplatforms for cancer theranostics
- Brucella: diagnosis, epidemiology, treatment
- Mobile Learning in Education
- Teaching and Learning Programming
- Retinoids in leukemia and cellular processes
- History and advancements in chemistry
- Nitric Oxide and Endothelin Effects
- Porphyrin and Phthalocyanine Chemistry
- Synthesis and Characterization of Heterocyclic Compounds
Université de Montpellier
2016-2025
Institut des Biomolécules Max Mousseron
2016-2025
École Nationale Supérieure de Chimie de Montpellier
2015-2024
Centre National de la Recherche Scientifique
2015-2024
Hôpital Émile-Roux
2018
Centre Occitanie-Montpellier
2018
University of Florence
2003-2014
Georgetown University
1999-2014
University of Geneva
1999-2014
Toronto General Hospital
2011
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...
A series of 7-substituted coumarins incorporating various glycosyl moieties were synthesized and investigated for the inhibition zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). These very weak or ineffective as inhibitors housekeeping, off target isoforms CA I II, but some them inhibited tumor-associated IX XII in low nanomolar range. They also significantly growth primary tumors by highly aggressive 4T1 syngeneic mouse mammary tumor cells at 30 mg/kg, constituting interesting candidates...
Sulfur-containing functional groups are privileged motifs that occur in various pharmacologically effective substances and several natural products. Various functionalities found with a sulfur atom at diverse oxidation states, as illustrated by thioether, sulfoxide, sulfone, sulfonamide, sulfamate, sulfamide functions. They valuable scaffolds the field of medicinal chemistry part large array approved drugs clinical candidates.Herein, authors review current research on development...
Sulfonamides inhibit the catalytic activity of carbonic anhydrases (CAs, EC 4.2.1.1), enzymes participating in regulation acid−base balance and ion transport many tissues. Carbonic anhydrase IX (CA IX), a transmembrane isoform with predominant association tumors limited distribution normal tissues, is strongly overexpressed by hypoxia. Hypoxia increases performance CA contributing to microenvironmental acidosis, which influences cancer progression treatment outcome. represents target for...
A panel of compounds belonging to the underexposed sulfamate class carbonic anhydrase (CA, EC 4.2.1.1) inhibitors was generated that displayed high specificity at nanomolar levels for tumor-associated CA IX/XII isoforms. Three specific showed a positive response in vitro assays tumor cell migration and spreading. One them, 4-(3′-(3″,5″-dimethylphenyl)ureido)phenyl (S4), taken forward into orthotopic MDA-MB-231 (breast carcinoma) model mice. Treatment with 10 mg/kg maintenance dosage S4 given...
A series of sulfamates or bis-sulfamates incorporating aliphatic, aromatic, polycyclic (steroidal), and sugar moieties in their molecules has been synthesized assayed as inhibitors the zinc enzyme carbonic anhydrase (CA), more precisely cytosolic isozymes CA I andII, transmembrane, tumor-associated IX. Some these compounds were previously reported to act steroid sulfatases, among which estrone sulfatase (ES) dehydroepiandrosterone (DHEAS) are key therapeutic targets for estrogen-dependent...
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)...
An approach for the synthesis of carbonic anhydrase (CA, EC 4.2.1.1) inhibitor coated gold nanoparticles is reported. This nanomaterial selectively inhibited tumor-associated isoform CA IX overexpressed in hypoxic cancers over ubiquitous, cytosolic housekeeping isozymes I and II was membrane impermeant. As has an extracellular active site, new which confined to space may be useful imaging treatment tumors.
A β-carbonic anhydrase (CA, EC 4.2.1.1) from the bacterial pathogen Brucella suis, bsCA 1, has been cloned, purified, and characterized kinetically. 1 appreciable activity as catalyst for hydration of CO2 to bicarbonate, with a kcat 6.4 × 105 s−1 kcat/Km 3.9 107 M−1·s−1. panel 38 sulfonamides one sulfamate have investigated inhibition this new β-CA. All types activities detected, KIs in range 17 nM 5.87 μM. The best inhibitors were ethoxzolamide (17 nM), celecoxib (18 dorzolamide (21...
Reaction of 6-/7-hydroxycoumarin with metronidazole afforded conjugates which incorporate two interesting chemotypes may inhibit carbonic anhydrases (CAs, EC 4.2.1.1) due to the presence coumarin moiety and possess radiosensitizing effects nitroazole. Another dual action compound, act both as CA inhibitor well monocarboxylate transporter inhibitor, is 3-cyano-7-hydroxy-coumarin. These compounds have been investigated inhibitors 11 human isoforms. Submicromolar inhibition was observed against...
Background and purposeCarbonic anhydrase IX (CAIX) plays an important role in pH regulation processes critical for tumor cell growth metastasis. We hypothesize that a dual targeting bioreductive nitroimidazole based anti-CAIX sulfamide drug (DH348) will reduce sensitize tumors to irradiation CAIX dependent manner.Material methodsThe effect of the its single control drugs on extracellular acidification radiosensitivity was examined HT-29 colorectal carcinoma cells. Tumor time reach 4× start...