Glaucoma is a serious disease, which increases intraocular pressure in the eye and can lead to blindness. New compounds have been designed to reduce intraocular pressure, reveals a new study.
One of the ways to treat glaucoma is to reduce aqueous humour secretion in the ciliary body of the eye by suppressing (inhibiting) activity of special enzymes carbonic anhydrases.
Glaucoma
Glaucoma is a group of disorders involving the optic nerve, often associated with a rise in intraocular pressure. Uncontrolled glaucoma can lead to blindness.
Advertisement
‘New compounds designed can reduce intraocular pressure inside the eye and can aid in the development of new antiglaucoma drugs.’
Tweet it Now
Russian scientists from RUDN University have designed new compounds that can effectively reduce intraocular pressure by isoform selective inhibiting human carbonic anhydrase.
The results of the study were published in the prestigious Bioorganic Chemistry journal.
The study is focused on benzenesulfonamide derivatives containing a 1,2,4-oxadiazole moiety. "It was the first time that these compounds were considered as potential inhibitors of human carbonic anhydrase. Managing the enzyme's activity in ciliary processes using this compounds we can normalize the intraocular pressure," says Anton Shetnev, one of the authors of the paper from RUDN University.
![Cataract]( "Cataract")
A cataract is cloudiness in the crystalline lens of the eye that results in a gradually progressive painless diminution of vision.
Carbonic anhydrases comprise a family of widespread enzymes that facilitate CO2-bicarbonate interconversion in all tissues of human body. Their function is to catalyze the reversible hydration of carbon dioxide, which produces bicarbonate anion and a proton.
This simple biochemical reaction is central to regulating pH in the intra- and extracellular space in various tissues and organs. It should be noted that carbonic anhydrase in performed by 15 isoforms (isoenzymes) localized in various tissues and slightly differing in the active site architecture.
Sulfonamide-based inhibitors bind to the prosthetic zinc-ion in the catalytic cavity, thussuppressing activity of the enzyme which can be described as a "key-lock" interaction. Most of known carbonic anhydrase inhibitors can be compared to a master key which relatively roughly opens any lock-enzyme (all isoforms)of the corresponding family.
Since the affinity is non-selective (that is, there is no key thread exactly entering the grooves), such an agent might cause plenty of undesired effects. When developing a drug candidate, either potency of selectivity of the inhibitor are crucial.
The latter could be achieved by designing sulfonamide-incorporating small-molecules bearing appropriate molecular periphery.
Our study shows that by attaching substituted oxadiazole ring to the benzenesulfonamide fragment substantional improvement in potency and selectivity of the inhibition can be achieved, thus suggesting this scaffold to be promising for the development of new antiglaucoma drugs.
"We are now to continue improving the selectivity of our inhibitors on the next stages of our work: we need to conduct research aimed at further modification of the compounds in order tomaximize affinity only to the target isoforms, regulating intraocular pressure, which is a great challenge" Anton Shetnev concludes.
Source: Eurekalert
The study is focused on benzenesulfonamide derivatives containing a 1,2,4-oxadiazole moiety. "It was the first time that these compounds were considered as potential inhibitors of human carbonic anhydrase. Managing the enzyme's activity in ciliary processes using this compounds we can normalize the intraocular pressure," says Anton Shetnev, one of the authors of the paper from RUDN University.
Cataract
A cataract is cloudiness in the crystalline lens of the eye that results in a gradually progressive painless diminution of vision.
Advertisement
Carbonic anhydrases comprise a family of widespread enzymes that facilitate CO2-bicarbonate interconversion in all tissues of human body. Their function is to catalyze the reversible hydration of carbon dioxide, which produces bicarbonate anion and a proton.
This simple biochemical reaction is central to regulating pH in the intra- and extracellular space in various tissues and organs. It should be noted that carbonic anhydrase in performed by 15 isoforms (isoenzymes) localized in various tissues and slightly differing in the active site architecture.
Sulfonamide-based inhibitors bind to the prosthetic zinc-ion in the catalytic cavity, thussuppressing activity of the enzyme which can be described as a "key-lock" interaction. Most of known carbonic anhydrase inhibitors can be compared to a master key which relatively roughly opens any lock-enzyme (all isoforms)of the corresponding family.
Since the affinity is non-selective (that is, there is no key thread exactly entering the grooves), such an agent might cause plenty of undesired effects. When developing a drug candidate, either potency of selectivity of the inhibitor are crucial.
The latter could be achieved by designing sulfonamide-incorporating small-molecules bearing appropriate molecular periphery.
Our study shows that by attaching substituted oxadiazole ring to the benzenesulfonamide fragment substantional improvement in potency and selectivity of the inhibition can be achieved, thus suggesting this scaffold to be promising for the development of new antiglaucoma drugs.
"We are now to continue improving the selectivity of our inhibitors on the next stages of our work: we need to conduct research aimed at further modification of the compounds in order tomaximize affinity only to the target isoforms, regulating intraocular pressure, which is a great challenge" Anton Shetnev concludes.
Source: Eurekalert
Eye Pain Symptom Evaluation
Eye pain usually follows trauma, eye infection or inflammation of the eye and the surrounding structures. The cause of eye pain can be diagnosed based on the type of pain and associated symptoms.
Advertisement
Advertisement
|
Advertisement
Recommended Readings
Latest Research News
Experts consulted by GlobalData anticipate a significant overhaul in the Gaucher disease scenario because of forthcoming gene therapies in development.
Within the seven major markets, 12% to 20% of diagnosed prevalent NASH cases present severe liver damage (stage 4 liver fibrosis), denoting cirrhosis.
Memory deficits in individuals with epilepsy, especially cognitive difficulties, might partially stem from the transient impairments caused by these slow waves.
High altitude training exhibits potential benefits for pre-surgery patients, enhancing readiness, stated a new study.
The AI method shows promise in identifying imaging biomarkers for diagnosing ADHD.