Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0595921 (
intraocular pressure
)
11,750
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Four generations of poly(amidoamine) (PAMAM) dendrimers decorated with benzenesulfonamide moieties were prepared by derivatizing the amino groups of the dendrimer with 4-carboxy-benzenesulfonamide functionalities. Compounds incorporating 4, 8, 16, and 32 sulfonamide moieties were thus obtained, which showed an increasing carbonic anhydrase (CA, EC 4.2.1.1) inhibitory action with the increase of the number of sulfamoyl groups in the dendrimer. Best inhibitory activity (in the low nanomolar-subnanomolar range) was observed for isoforms
CA II
and XII, involved among others in glaucoma. In an animal model of this disease, the chronic administration of such dendrimers for 5 days led to a much more efficient drop of
intraocular pressure
compared to the standard drug dorzolamide.
...
PMID:Poly(amidoamine) Dendrimers with Carbonic Anhydrase Inhibitory Activity and Antiglaucoma Action. 2584 26
The design of three dual-tailed sulfonamide series
11a-11g
,
14a-14h
, and
16a-16e
as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors are presented. All compounds were evaluated for inhibitory action against pharmacologically relevant human CA isoforms I, II, IV, and VII. Compounds
11a-11g
emerged as potent CA inhibitors against the four tested isoforms with a significant selectivity to
CA II
, which is implicated in glaucoma (
K
i
in the range 0.36-6.9 nM). X-ray crystallographic analysis of three compounds (
11a
,
11d
, and
11g
) bound to
CA II
showed the validity of the adopted drug design strategy as specific moieties within the ligand structure interacted directly with the hydrophobic and hydrophilic halves of the
CA II
active site. Compounds
11b
-
11d
and
11g
were evaluated for their
intraocular pressure
-lowering effects in a rabbit model of glaucoma.
11b
and
11d
showed significant efficacy when compared to the clinically used drug dorzolamide.
...
PMID:Discovery of Potent Dual-Tailed Benzenesulfonamide Inhibitors of Human Carbonic Anhydrases Implicated in Glaucoma and in Vivo Profiling of Their Intraocular Pressure-Lowering Action. 3203 97
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