Chemists have synthesized new molecules that exhibit anti-cancer properties.

Scientists have developed a straightforward and accessible method for producing diazepines—molecules that are widely found among natural substances and pharmaceuticals. The researchers synthesized precursor molecules, and by heating them to 80 degrees Celsius in the presence of rhodium compounds, they were able to efficiently obtain a range of rare-class diazepines. The resulting products demonstrated the ability to inhibit the growth of cancer cells while minimally affecting the viability of healthy cells. This characteristic suggests their potential use in the development of anticancer agents.

2024-10-19 07:29:56https://naked-science.ru/article/column/molekuly-s-protivorakovoj

The results of the study, supported by a grant from the Presidential Program of the Russian Science Foundation (RSF), have been published in the journal Organic Letters.

Diazepines are organic molecules that feature a seven-atom ring structure comprising five carbon atoms and two nitrogen atoms. Their derivatives, particularly benzodiazepines, are widely utilized in medicinal chemistry. They form the basis for anticancer drugs as well as medications for anxiety, epilepsy, and depression. Due to the promising nature of diazepines, researchers are exploring methods to synthesize new types of such compounds.

Researchers from Saint Petersburg State University (Saint Petersburg) discovered a straightforward method for obtaining a rare class of diazepines that lack the additional ring typical of most compounds of this type. Initially, the authors synthesized precursor molecules from commercially available substances, consisting of two interconnected five-membered rings with additional chemical groups. They added a rhodium catalyst and heated the resulting mixtures for one and a half to four hours at temperatures ranging from 80°C to 130°C. As a result, a variety of different diazepines were produced.

Subsequently, the authors investigated the reaction mechanism both experimentally and through computational calculations. It was found that under the influence of rhodium compounds, the five-membered rings of the precursor molecules break down, merging into a single larger ring—the diazepine ring—via the intermediate formation of a three-membered ring. During this rearrangement, bonds between carbon atoms, as well as between nitrogen and oxygen, and between nitrogen and carbon, are broken. Understanding how this process occurs will be beneficial in the search for synthesis methods for other diazepine derivatives.

Although diazepines similar to those newly obtained have been known for over 30 years, their biological activity had not been studied previously. Co-authors of the study from Togliatti State University (Togliatti) examined how the obtained substances affect cells of breast, prostate, skin, lung, colorectal cancers, as well as healthy cells of lung connective tissue. It turned out that 10 compounds suppressed the growth of diseased cells to varying degrees, notably, seven of them did not affect healthy cells. This suggests that the substances obtained may hold promise for combating oncological diseases.

“The most common cyclic compounds are molecules with five- or six-membered cycles. Therefore, we were very surprised and pleased when we realized we had obtained products with a seven-membered cycle—diazepines. The proposed method for synthesizing such unique substances opens up new possibilities for developing anticancer drugs. In the future, we plan to apply rhodium catalysis to other precursor molecules and hope to obtain even more interesting and promising compounds,” says Nikolai Rostovsky, the project leader supported by the RSF grant, Doctor of Chemical Sciences, and Head of the Department of Organic Chemistry at Saint Petersburg State University.