Glaucoma is a serious disease associated with increased intraocular pressure which often leads to blindness. 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. 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 compoundswe can normalize the intraocular pressure," says Anton Shetnev, one of the authors of the paper from RUDN University.
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.
The research was carried out jointly with Saint Petersburg State University, Yaroslavl State Pedagogical University named after K.D. Ushinsky and Italian colleagues from University of Florence and University of Piza.
Valeriya V. Antonova | EurekAlert!
Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View
22.06.2018 | University of Sussex
New cellular pathway helps explain how inflammation leads to artery disease
22.06.2018 | Cedars-Sinai Medical Center
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
22.06.2018 | Materials Sciences
22.06.2018 | Earth Sciences
22.06.2018 | Life Sciences