‘Laser-induced twisting’: chemists discover a potential drug – a compound that changes its activity when exposed to light
Scientists from St Petersburg University, together with their colleagues from the St Petersburg Scientific Research Centre for Ecological Safety of the Russian Academy of Sciences, have discovered a new organic compound from the thiazolotriazole which changes its activity when exposed to light. It inhibits a key enzyme of the nervous system — cholinesterase, which is involved in the work of many systems of the human body.
Substances with this effect are used, for example, to treat Alzheimer’s disease or in ophthalmology. Their discovery will help to ‘turn off’ the biological activity of the drug using a laser. This means it will be possible to affect the cells of the human body more safely and precisely. The graphical abstract of the article is published on the cover of the scientific journal Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy.
Most existent drugs cannot be ‘turned on’ or ‘turned off’ at the behest of a doctor or patient: once you have taken a pill, it remains biologically active during the entire journey through the body and even after it. At present, for example, there is a problem of deactivation of antibiotics, which, after being consumed by humans, inevitably enter the environment and lead to the rapid development of antibiotic-resistant microorganism strains.
One of the possible ways to solve this problem is the development of photopharmacology. It is a fairly young field of pharmaceutics, which studies substances that can ‘turn on’ and ‘turn off’ when exposed to light. This approach will make it possible to ‘turn the drugs on’ when they reach the area of inflammation, or to ‘turn the biological activity of the drug off’ timely upon achieving the desired therapeutic outcome, or if the patient has adverse side effects. As a rule, photopharmacological agents consist of two parts: the drug itself and the photoactive ‘switch’. However, the researchers from St Petersburg University and their colleagues from the Scientific Research Centre for Ecological Safety of the Russian Academy of Sciences have managed to obtain a compound that simultaneously performs both functions. This is methyl 3-amino-2-methyl-3H-thiazolo[3,2-b][1,2,4]triazol-7-ylium-6-phosphonate.
When exposed to laser irradiation, the phosphonate group of a new organic compound rotates, which leads to its biological activity change.
‘This substance has been discovered partly by chance. It was first synthesised by our colleagues from the St Petersburg State Institute of Technology, when they were solving problems in the field of organic synthesis. Later, we carried out joint research in this group of substances. At some point, we measured the absorption spectrum and found out that if you shine into the absorption band of this compound with a laser with a certain wavelength (266 nanometres), it will change both the absorption spectrum and its biological activity. It turned out that the molecule changes its geometry: rotation of the phosphonate group occurs. This makes the compound change its biological activity and reduce the inhibiting ability towards cholinesterase. Moreover, after the light is «off», the substance remains stable, and its biological activity is not restored,’ said Alina Manshina, Doctor of Chemistry, Professor in the Department of Laser Chemistry and Laser Materials Science at St Petersburg University.
The chemists demonstrated an unusual transformation in the graphical abstract of their article. The picture shows a couple dancing a twist, and the girl is under the spotlight, which symbolises laser irradiation. The editors of the journal decided to put the ‘laser twisting’ on the cover of the issue.
Although research in photopharmacology is currently carried out only on laboratory animals, this field does open up great prospects for treating humans. A ‘switchable’ cholinesterase inhibitor can be used in the future, for example, in ophthalmology: similar substances, but without a light ‘switch’, are currently being used to reduce ocular tension. Another area of potential use of phosphorus functionalised thiazolotriazole is for treating Alzheimer’s disease and other neurodegenerative diseases.
‘This discovery enables us to set many new challenges. How to visualise the area where the drug has been absorbed? How to determine the concentration of this drug? How to obtain sufficient biological activity? How to find «switches» that not only «turn off» but also «turn on» active substances? In fact, this is the topic of our new research. We are currently working with compounds that, when exposed to light, on the contrary, begin to show more pronounced biological activity. They have both a medical and a photoactive component,’ said Alina Manshina.
The research team included scientists from: the ‘Laser Synthesis’ scientific group headed by Alina Manshina, Professor in the Department of Laser Chemistry and Laser Materials Science at the Institute of Chemistry, St Petersburg University; the St Petersburg Scientific Research Centre for Ecological Safety of the Russian Academy of Science; and the Resource Centre for Optical and Laser Materials of the St Petersburg University Research Park.
Article: «Laser-induced twisting of phosphorus functionalized thiazolotriazole as a way of cholinesterase activity change», Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 246 (2021) 118979.