Molecules that inhibit the effects of a common anticoagulant medication are synthesized by a team

Molecules that inhibit the effects of a common anticoagulant medication are synthesized by a team ...

A study conducted by researchers from the Spanish National Research Council (CSIC) has discovered and synthesized several molecules that inhibit the effect of the most common anticoagulant medication. This medication is very useful for treating patients at risk of thrombi, but on many occasions it is essential to avoid surgical interventions, according to a study conducted with mice. These findings have been published in the journal of Medicinal Chemistry.

The proof of concept was published in the journalAngewandte Chemie International Edition in 2018 in which the researchers used Dynamic Combinatorial Chemistry (DCC) systems and achieved a simple chemical that in vitro inhibited the effect of heparin, the most widely used anticoagulant medication. In this study, the team led by Ignacio Alfonso, who from the Institute for Advanced Chemistry of Catalonia, has used the same technology for a more broad screening, which has allowed them

Heparin is widely used in clinical, mostly as an anticoagulant, but also as an antiviral and anticancer agent. In addition, it is being revitalized even more with the covid-19 epidemic, which is currently being used as a preventive treatment for clots produced in coronavirus patients and pregnant women. "Although it is one of the most common anticoagulant medications, it is not free of dangers, and it is vital to have a well-rounded battery of antid

Patients at risk of blood clots are often affected by allergic reactions or overdose, which are likely to result in significant bruising or even uncontrolled bleeding, according to the researcher. In these instances, the inhibition of circulating heparin in the bloodstream is essential to prevent complications due to excessive bleeding, according to Alfonso.

Protamine sulfate is currently the antidote that exists to neutralize the action of heparin, but it is a high molecular weight medication, which is therefore potentially harmful to the environment. To date, there is no small molecule on the market that suppresses the anticoagulant effect of heparin. According to Alfonso, the physicochemical properties of this anionic polysaccharide.

The new approach, based on dynamic combinatorial chemistry, has been used once more, which involves the selection, identification, and preparation of molecules for a specific application in a single phase, accelerating the development of new functional compounds. Due to limited structural information and the heterogeneity of the heparin molecule, this technique is a good candidate as a model in dynamic combinatorial chemistry, since it does not require extensive knowledge of the structure of the target molecule.

The results from this research show the effectiveness of this methodology. Moreover, an excellent correlation between screening results and heparin inhibition was found with in vitro enzymatic experiments, from which a small collection of molecules with excellent activity was obtained. Two of these results, which were then tested in vivo, thus achieving satisfactory results. "This study represents a definitive validation of our approach," Alfonso said.

A robust combinatorial chemistry methodology has been shown to be a useful tool for identifying new milestones in future drug development, especially if conventional approaches have deemed it difficult to achieve.

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