Chemists develop a method for synthesizing compounds for pharmaceutical products

A team of chemists from RUDN University has suggested a universal method for synthesizing thienoindolysine derivatives. Due to their special properties, these substances can be used to produce antibacterial and anticancer drugs, as well as new materials for optoelectronics. The results of the study were published in Chemical selection magazine.

Thienoindolizines are tricyclic compounds containing sulfur and nitrogen heteroatoms. Thienoindolizines are combinations of two structural elements: thiophene and indolysine. Both of these substances have many important biological characteristics, such as anticancer and antibacterial properties. Thienoindolizines are used not only in biomedicine but also in optoelectronics to create new materials. However, the existing synthesis methods only work for a small group of starting substances and cannot guarantee the presence of any group of functional atoms in the product. A team of chemists from RUDN University was the first to suggest a universal approach to thienoindolizine synthesis based on two- and three-component thienopyridine reactions.

“Currently, there are no universal methods for the synthesis of thienoindolizine derivatives that would not only form the structure of a compound, but would also allow for the addition of several functional substituents. Therefore, researchers focus on inexpensive and moderate approaches to creating of thienoindolysis structures from simple precursors, “explained Alexander Titov, Ph.D., and lecturer in the Department of Organic Chemistry, RUDN University.

The team based the synthesis reaction on compounds from the group of heterocycles with sulfur and nitrogen atoms: derivatives of thienopyridine. In order for them to turn into thienoindolizines, they required an additional cycle and the addition of different functional groups. Scientists studied the reactions of thienopyridine derivatives with substances of six different groups: alkynes, aldehydes, alcohols and other organic compounds.

The RUDN team tested different reaction conditions for different reagents: microwave radiation, inert atmosphere, solvents, catalysts, different temperatures in the 140-150 ° C range and different reaction times, from 10 minutes to several hours. As a result, they managed to obtain 28 thienoindolysine derivatives. For some of them, the team identified optimal synthesis conditions that guaranteed a high yield of 70% or more. Without the proper catalysts and conditions, the yield remained at the 10-20% level.

Seven of the compounds obtained were tested for their ability to kill cancer cells or for cytotoxicity. Compared to existing chemotherapy drugs, the activity of these substances was insignificant. However, three of them had cytotoxic properties and required further research. The study of the antibacterial activity of the compounds obtained led to similar results: one substance out of six proved effective against hay bacillus and Candida fungi.

“The synthetic and biological aspects of thienoindolizines remain largely underestimated. We believe that a combination of two biologically active substances in one molecule must have its advantages. We will continue to develop new methods to synthesize these substances and control their characteristics. In the future, we will we look forward to developing a family of heterocyclic compounds with known anticancer, antibacterial and pain relieving properties, “added Alexander Titov, Ph.D., and lecturer in the Department of Organic Chemistry, RUDN University.