1,513 research outputs found
Bacterial Carbonic Anhydrases as Drug Targets: Toward Novel Antibiotics?
Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes which catalyze the hydration of carbon dioxide to bicarbonate and protons. Many pathogenic bacteria encode such enzymes belonging to the α-, β-, and/or γ-CA families. In the last decade, the α-CAs from Neisseria spp. and Helicobacter pylori as well as the β-class enzymes from Escherichia coli, H. pylori, Mycobacterium tuberculosis, Brucella spp., Streptococcus pneumoniae, Salmonella enterica, and Haemophilus influenzae have been cloned and characterized in detail. For some of these enzymes the X-ray crystal structures were determined, and in vitro and in vivo inhibition studies with various classes of inhibitors, such as anions, sulfonamides and sulfamates reported. Although efficient inhibitors have been reported for many such enzymes, only for Neisseria spp., H. pylori, B. suis, and S. pneumoniae enzymes it has been possible to evidence inhibition of bacterial growth in vivo. Thus, bacterial CAs represent promising targets for obtaining antibacterials devoid of the resistance problems of the clinically used such agents but further studies are needed to validate these and other less investigated enzymes as novel drug targets
Enzyme Inhibition and more--a tribute to John Smith.
When John Smith founded Journal of Enzyme Inhibition in 1985, there were only a few journals publishing interdisciplinary papers on medicinal/pharmaceutical chemistry. Since it focused on a niche a..
Metal Complexes of 1,3,4-Thiadiazole-2,5-Disulfonamide are Strong Dual Carbonic Anhydrase Inhibitors, although the Ligand Possesses very Weak such Properties
Coordination compounds of Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) with 1,3,4-thiadiazole-2,5-disulfonamide as ligand were synthesized and characterized by IR and UV spectroscopy, conductimetry and
thermogravimetry. The parent ligand is a very weak carbonic anhydrase (CA) inhibitor, although it
constituted the lead for developing important classes of diuretics. The complex derivatives behave as much
stronger CA inhibitors, with IC50 values around 10−8M against isozyme CA II, and 10−7 M against isozyme
CAI
Special Issue: Sulfonamides
The sulfonamides and their structurally related derivatives, such as the sulfamates and sulfamides, possess the general formula A-SO2NHR, in which the functional group is either directly bound to an aromatic, heterocyclic, aliphatic, or sugar scaffold (of type A), or appended to such a scaffold via a heteroatom, most frequently oxygen or nitrogen (leading thus to sulfamates and sulfamides, respectively) [...
Complexes With Biologically Active Ligands. Part 1. Synthesis of Coordination Compounds of Diazoxide With Transition- and Main-Group Cations
Complexes of diazoxide (3-methyl-7-chloro-1,2,4-benzothiadiazine-1,1-dioxide) - an antihypertensive
and hyperglycemic pharmacological agent - with a series of transition- and main-group di-, triand
tetravalent metal ions were prepared and characterized by elemental analysis, spectroscopic,
thermogravimetric, magnetic and conductimetric measurements. The complexes were tested as inhibitors of
the enzyme carbonic anhydrase (CA), proving modest activity towards CA II and better inhibition of CA I
Complexes With Biologically Active Ligands. Part 2. Preparation of Copper(II) Complexes of Positively-Charged Derivatives of Aminoglutethimide
Cu(II) complexes of 1-[4-(3-ethyl-piperidine-2,6-dione)-3-yl]-phenyl-2,4,6-trisubstituted
pyridinium perchlorates, containing alkyl, aryl and combinations of these two types of moieties in their
molecule were synthesized and characterized by elemental analysis, spectroscopy, magnetic,
thermogravimetric and conductimetric measurements. In these complexes, Cu(II) ions are in octahedral
geometry with four water molecules occupying the equatorial coordination sites and the two organic ligands
in deprotonated state the remaining axial ones. The donor atom of these ligands is constituted by the ionized
nitrogen of the glutarimide moiety. The new derivatives possess weak inhibitory activity towards the zinc
enzyme carbonic anhydrase
Thienothiopyransulfonamides as Complexing Agents for the Preparation of Dual Carbonic Anhydrase Inhibitors
Co(II); Zn(II) and Cu(II) complexes of two new sulfonamide carbonic anhydrase (CA) inhibitors,
derivatives of thienothiopyran-2-sulfonamide, were prepared and characterized by analytic, spectroscopic,
magnetic and conductimetric measurements. The new complexes are more potent CA inhibitors than the
parent sulfonamides, with IC50
values around 0.1 nM, against isozyme CA II
Complexes With Biologically Active Ligands. Part 4. Coordination Compounds of Chlorothiazide With Transition Metal Ions Behave as Strong Carbonic Anhydrase Inhibitors
Complexes of the diuretic benzothiadiazine derivative chlorothiazide (6-chloro-7-sulfamoyl-
1,2,4-benzothiadiazine-1,1-dioxide) with V(IV); Fe(II); Co(II); Ni(II); Cu(II), Ag(I) and U(VI) were
prepared and characterized by elemental analysis, spectroscopic, thermogravimetric, magnetic and
conductimetric measurements. The complexes behave as effective inhibitors for two isozymes (I and II) of
carbonic anhydrase (CA)
3D-QSAR CoMFA studies on sulfonamide inhibitors of the Rv3588c β-carbonic anhydrase from Mycobacterium tuberculosis and design of not yet synthesized new molecules
AbstractThe human pathogen Mycobacterium tuberculosis contains three β-carbonic anhydrases (CAs, EC 4.2.1.1) in its genome. Inhibition of some of these CAs was shown to modulate the growth of M. tuberculosis. 3D-QSAR Comparative molecular field analyses (CoMFA) were carried out on inhibitors of the enzyme Rv3588c (also denominated mtCA 2). A series of sulfonamides known to inhibit mtCA 2, including some diazenylbenzenesulfonamides, was considered in our study. The predictive ability of the model was assessed using a test set of seven compounds. The best model has demonstrated a good fit having predictive r2 value of 0.93 and cross-validated coefficient q2 value as 0.88 in tripos CoMFA region. Our results indicate that the steric and electrostatic factors play a significant role in mtCA 2 inhibition for the investigated compounds. We proposed nine new not yet synthesized mtCA 2 inhibitors, all of them probably with significantly improved anti-Rv3588c inhibitory activity
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