- Статьи
- Science and technology
- Nitrogen and he: scientists have found an effective replacement for popular heart medications
Nitrogen and he: scientists have found an effective replacement for popular heart medications
Scientists have synthesized an iron complex that can become a more effective and safe alternative to nitroglycerin and other drugs for the treatment of cardiovascular diseases. The resulting compounds are capable of releasing nitric oxide for a long time, a substance that plays a key role in the functioning of the vascular system.: it helps to relax the walls of blood vessels, reduce pressure and prevents the formation of blood clots. Due to the gradual release of the active substance, it will potentially be possible to reduce the dosage of drugs, reduce the risk of side effects and avoid addiction. However, according to experts, the development will have to go through all the necessary testing stages for practical application.
What does nitric oxide do in the body?
Scientists from the Federal Research Center for Problems of Chemical Physics and Medical Chemistry of the Russian Academy of Sciences have synthesized an iron complex that can form the basis of promising drugs for hypertension and thrombosis. Its main feature is that it contains reactive groups of nitric oxide (compounds of nitrogen with oxygen), which can be released in the body without additional activation. This substance plays an important role in the functioning of the cardiovascular system.: it helps to relax the walls of blood vessels and thereby avoid high blood pressure. In addition, the molecule prevents the formation of blood clots.
Discussion of experimental data
However, in some cases, its synthesis in the body is disrupted, and a lack of this substance leads to hypertension, heart failure and other diseases, the scientists said. In these cases, doctors use drugs that artificially make up for the deficiency, such as nitroglycerin. However, existing medications cause side effects, the development of tolerance (addiction) and are short-lived, which is why patients need to take pills regularly. Therefore, scientists are looking for safer compounds with long-lasting effects.
To solve this problem, the scientists investigated the properties of the three iron complexes obtained and found that they begin to release nitric oxide immediately after dissolution, but they do so gradually. The slowest decay, over several days, was observed when using the compound with the longest carbon chain between the iron center and the phenyl ring (a ring of carbon atoms).
"This structure slowed down the decomposition of the molecule: the complex gradually released nitric oxide, and the resulting intermediates remained stable in solution for a long time," explained Olesya Ostrovova, project leader and a leading researcher at the Federal Research Center for Chemical Physics and Medicinal Chemistry of the Russian Academy of Sciences.
Discussion of experimental data
Experiments with cell cultures showed that the complex with the longest decay time turned out to be the safest: it did not reduce cell viability even at concentrations exceeding those of the other two compounds by four and 1.13 times, respectively. Therefore, it can potentially form the basis of nitric oxide donor drugs with a longer duration of action than existing drugs.
— In the future, we plan to study the obtained compounds on experimental animals. In addition, we will continue to develop and study the properties, including the biological activity and rate of release of nitric oxide from other compounds of this series," said Olesya Ostrovova.
The effect of a smart dropper
Nitric oxide is an internal "vasodilator", and when there is a shortage of it, the heart works hard. The problem with old drugs like nitroglycerin is that they act like an ambulance: quickly, but for a short time, plus the body gets used to it and asks for more and more doses, molecular biologist Arina Kholkina told Izvestia.
— New iron complexes are more like a "smart dropper". They release nitric oxide gradually, over several days, without additional activation and without toxicity to cells. Of course, the introduction of new drugs in pharmacies is still a long way off, as animal testing is needed. The very idea of "long and safe allocation of NO" looks very promising. Especially for patients with hypertension and heart failure, who now have to take pills several times a day," the specialist noted.
Study of biological activity of nitrosyl iron complexes
Despite its important physiological role, the practical use of nitric oxide is limited: it is extremely unstable and rapidly degrades. Therefore, donors of nitric oxide are used in medicine — compounds capable of releasing it in the body. A classic example is nitroglycerin. However, such drugs act quickly, but for a short time, and their effect is difficult to maintain at a stable level with long-term therapy, said Alexander Bykov, Director of Healthcare Economics at R-Pharm Group of Companies.
— Russian scientists have proposed an alternative approach — the use of iron complexes that are simultaneously able to participate in the regulation of vascular processes and iron deficiency. In these compounds, nitric oxide is chemically bonded to iron and embedded in a more stable molecular structure. This allows not only to stabilize nitric oxide, but also to control its release due to the structural features of the complex and environmental conditions," he said.
For some compounds, the release continues for several days. From a practical point of view, this is fundamentally important: a slower and more controlled release allows for a stable vascular effect without sudden fluctuations in concentration. This can reduce the frequency of taking medications without losing effectiveness, the specialist emphasized.
Synthesis of nitrosyl iron complexes and investigation of their structure
If the claimed properties are confirmed in preclinical and clinical studies, it will be possible to talk about the creation of a new group of drugs with a long-lasting and predictable therapeutic effect, as well as a potentially better safety profile. This could be an important step in the treatment of conditions associated with nitric oxide deficiency, said Alexander Bykov.
The results of the study, supported by a grant from the Russian Science Foundation (RSF), are published in the Journal of Inorganic Biochemistry.
Переведено сервисом «Яндекс Переводчик»
