Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct.

@article{Temperini2008CarbonicAI,
  title={Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct.},
  author={Claudia Temperini and Alessandro Cecchi and Andrea Scozzafava and Claudiu T. Supuran},
  journal={Bioorganic \& medicinal chemistry letters},
  year={2008},
  volume={18 8},
  pages={
          2567-73
        }
}
Diuretics such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide, and bumetanide containing primary sulfamoyl moieties were reevaluated as inhibitors of 12 human carbonic anhydrases (hCAs, EC 4.2.1.1). These drugs considerably inhibit (low nanomolar range) some CA isozymes involved in critical physiologic processes, among the 16 present in vertebrates, for example, metolazone against CA VII, XII, and XIII, chlorthalidone against CA VB… Expand
Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference.
TLDR
The newly evidenced binding modes of these diuretics may be exploited for designing better CA II inhibitors as well as compounds with selectivity/affinity for various isoforms with medicinal chemistry applications. Expand
Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic and X-ray crystallographic studies.
TLDR
Different orientations of the bound sulfamates within the enzyme cavity were observed, which account for their distinct inhibition profiles, and CA II/IX potent inhibitors belonging to the sulfamate class are valuable clinical candidates with potential for development as antitumor agents with a multifactorial mechanism of action. Expand
Carbonic anhydrase inhibitors. Diazenylbenzenesulfonamides are potent and selective inhibitors of the tumor-associated isozymes IX and XII over the cytosolic isoforms I and II.
TLDR
Since CA IX/XII were recently shown to be both therapeutic and diagnostic targets for hypoxic solid tumors overexpressing these proteins, such compounds held promise for the management of hypoxic tumors, which are largely non-responsible to classical chemo- and radio-therapy. Expand
Carbonic anhydrase inhibitors; fluorinated phenyl sulfamates show strong inhibitory activity and selectivity for the inhibition of the tumor-associated isozymes IX and XII over the cytosolic ones I and II.
TLDR
A series of fluorinated-phenylsulfamates prepared by sulfamoylation of the corresponding phenols and the inhibition of four physiologically relevant carbonic anhydrase isozymes are investigated, finding them interesting candidates for targeting hypoxic tumors overexpressing CA IX and/or XII. Expand
Carbonic anhydrase inhibitors. Biphenylsulfonamides with inhibitory action towards the transmembrane, tumor-associated isozymes IX possess cytotoxic activity against human colon, lung and breast cancer cell lines
Reaction of 4,4-biphenyl-disulfonyl chloride with aromatic/heterocyclic sulfonamides also incorporating a free amino group, such as 4-aminobenzenesulfonamide, 4-aminoethyl-benzenesulfonamide,Expand
Carbonic anhydrase inhibitors as diuretics
Abstract Several human carbonic anhydrase (CA) isoforms, namely hCA II, IV, VB, XII, and XIV, are expressed in many segments of the human nephron, the functional unit of the kidney. Acetazolamide andExpand
Carbonic Anhydrase II as Target for Drug Design
Abstract Inhibition of CA II has pharmacological applications in the field of antiglaucoma and diuretic agents, for the treatment of altitude sickness, for some anticonvulsants, and probably againstExpand
New chemotypes acting as isozyme-selective carbonic anhydrase inhibitors with low affinity for the offtarget cytosolic isoform II.
TLDR
It is demonstrated that a rather wide range of structures show low nanomolar-micromolar inhibitory activity against many CA isozymes, without inhibiting significantly the offtarget isoform CA II. Expand
Coumarins incorporating hydroxy- and chloro-moieties selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the cytosolic ones I and II.
TLDR
6-Hydroxycoumarin showed K(I)s >100 microM against CA I and II, being thus a selective, efficient inhibitor for the tumor-associated over cytosolic isoforms, and excellent leads for designing isoform-selective enzyme inhibitors. Expand
Phenylethynylbenzenesulfonamide regioisomers strongly and selectively inhibit the transmembrane, tumor-associated carbonic anhydrase isoforms IX and XII over the cytosolic isoforms I and II.
TLDR
A series of compounds incorporating regioisomeric phenylethynylbenzenesulfonamide moieties investigated for the inhibition of four human carbonic anhydrase isoforms found the position of the sulfamoyl group with respect to the alkyne functionality, and the nature of the moieties substituting the second aromatic ring were the principal structural features influencing CA inhibition. Expand
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References

SHOWING 1-10 OF 41 REFERENCES
Carbonic anhydrase inhibitors. Inhibition of the human cytosolic isozyme VII with aromatic and heterocyclic sulfonamides.
TLDR
Evidence is furnished that hCA VII is the isozyme responsible for the anticonvulsant/antiepileptic activity of sulfonamides and sulfamates, with high affinity for all the investigated compounds. Expand
Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides-a new target for the design of antitumor and antiglaucoma drugs?
TLDR
Apparently, hCA XII is a target of the antiglaucoma sulfonamides, and potent hCA XI inhibitors may be developed/used for the management of hypoxic tumors, together with inhibitors of the other tumor-associated isozyme, CA IX. Expand
Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV.
TLDR
The X-ray structure of the complex of topiramate with hCA II has been solved and it revealed a very tight association of the inhibitor, with a network of seven strong hydrogen bonds fixingTopiramate within the active site, in addition to the Zn(II) coordination through the ionized sulfamate moiety. Expand
Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides.
TLDR
There are important differences of affinity of these sulfonamides/sulfamates for the three transmembrane CA isozymes, with CA XII showing the highest affinity, followed by CA IX, whereas CA XIV usually showed the lowest affinity for these inhibitors. Expand
Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with EMATE, a dual inhibitor of carbonic anhydrases and steroid sulfatase.
The X-ray crystal structure for the adduct of human carbonic anhydrase II (hCA II) with estrone-3-O-sulfamate (EMATE), an antiendocrine agent showing both CA and estrone sulfatase inhibitoryExpand
Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with the antipsychotic drug sulpiride.
TLDR
The X-ray crystal structure for the adduct of human carbonic anhydrase (hCA) II with sulpiride, a sulfonamide derivative clinically used as antipsychotic drug, has been resolved and one unprecedented hydrogen bond involving the imino moiety of the carboxamido group of sulPiride and a water molecule was observed. Expand
Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies.
The antiepileptic drug zonisamide was considered to act as a weak inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) (with a K(I) of 4.3 microM against the cytosolic isozyme II). HereExpand
Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides.
The first inhibition study of the mitochondrial isozyme carbonic anhydrase (CA) V (of murine origin) with a series of aromatic and heterocyclic sulfonamides is reported. Inhibition data of theExpand
Carbonic anhydrase inhibitors: inhibition of human, bacterial, and archaeal isozymes with benzene-1,3-disulfonamides--solution and crystallographic studies.
Three benzene-1,3-disulfonamide derivatives were investigated for their interaction with 12 mammalian alpha-carbonic anhydrases (CAs, EC 4.2.1.1), and three bacterial/archaeal CAs belonging to theExpand
Carbonic anhydrase inhibitors: X-ray and molecular modeling study for the interaction of a fluorescent antitumor sulfonamide with isozyme II and IX.
The X-ray crystal structure of the fluorescent antitumor sulfonamide carbonic anhydrase (CA, EC, 4.2.1.1) inhibitor (4-sulfamoylphenylethyl)thioureido fluorescein (1) in complex with the cytosolicExpand
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