Chemists propose another domino response to deliver organic compound against cancers

Overview

• Post By : Kumar Jeetendra


• Source: RUDN University


• Date: 12 Oct,2020

A group of chemists in RUDN University suggested a new response to produce organic compounds in 1 vessel. The end products proven to be effective against the cells of carcinomas, including drug-resistant ones. The new reaction was explained from the Bioorganic Chemistry journal.

For many organic substances synthesis is a multistage process of step-by-step molecule assembly. At each stage, only one chemical bond is formed. After each step, the product is processed and used in the next response. Domino reactions are a cascade of reactions that happen one after another in one vessel with no additional reagents. Similar compounds are used as anti inflammatory and antitumor drugs, and some of them can potentially treat Alzheimer’s disease.

The group proposed using salicylaldehyde (a derivative of salicylic acid) and homophthalonitrile and catalyzing the reaction with ammonium formate that’s cheap and eco-friendly. The initial reagents were mixed with water and isopropyl alcohol and put into a microwave reactor where the mixture was heated up to 150°C for 20 minutes. The researchers used salicylaldehydes with unique substituents and because of this, received 19 derivatives of chromenoisoquinolineamines with 43-85% returns of various reaction products.

To analyze the health potential of the new substances, the chemists analyzed their effect on human cancerous cells. Cisplatin that’s used in chemotherapy and is proven to kill tumor cells was taken as a standard for comparison. The team chose the cells of breast and colon cancers, as well as three strains of ovary cancer cells (two of which were cisplatin-resistant) for the evaluation. All new substances proven to be poisonous for tumor cells, including the resistant strains. The researchers selected two compounds that proved to be efficient even in low concentrations and conducted computer modeling. According to it, the reason for their efficacy was an additional amine group that creates a stable bond with the nucleotides of the cancer cells DNA.

In our work, we searched for new compounds with promising therapeutic properties, as well as for ways to synthesize them. Our approach allows for the synthesis of tumor-combating substances in the course of one domino reaction that is extremely efficient: four new bonds are created within one synthetic operation. We worked together with our Italian partners, and the study was supported by the Russian Science Foundation. In the future, we plan to improve our methodology and develop three- and four-component reactions on its basis.”  -Alexey Festa, a Candidate of Chemical Sciences, and senior lecturer at the Department of Organic Chemistry, RUDN University