A new method for incorporating a single nitrogen atom into molecules has the potential to revolutionize drug development. Developed by researchers at the University of Oklahoma, this innovative approach could add to the diversity of compound libraries, perhaps leading the way for better treatments for diseases such as cancer and neurological disorders.
Nitrogen atoms and nitrogen-containing chemical structures, known as heterocycles, play a crucial role in medicinal chemistry. Notably, 85% of all FDA-approved drugs contain at least one nitrogen atom. Heterocycles are so essential to drug design that 75–80% of the top 200 brand-name drugs available on the market utilize these structures.
Researchers in this study used skeletal editing to integrate a single nitrogen atom into bioactive molecules. The present method allows a short-lived chemical intermediate, sulfenylnitrene, to be introduced into complex bioactive molecules to create new pharmacophores: different structural frames with diverse drug-like characteristics.
Such a switch may open new avenues in the search for pharmaceuticals by increasing the chemical diversity of known molecules without changing their central function.
Scientists drew a clear picture of how nitrogen oxides are formed
“We’re not starting from scratch. We are renovating existing molecules instead of creating entirely new molecules,” said OU associate professor Indrajeet Sharma. “By adding a single nitrogen atom to an existing structure, we can alter the molecule’s biological and pharmacological properties in meaningful ways, thus unlocking new therapeutic potential.”
The ability to add nitrogen atoms selectively to drug candidates at the later stages of development is a eureka moment, offering a far more efficient path for the discovery of drugs. Sharma’s is particularly notable for being additive-free and metal-free; thus, it can be applied to various functional groups within a molecule, which are critical for pharmaceutical applications.
This new technique can potentially cut the cost and time required to bring new drugs to market. Traditional drug development is a complex and expensive process, but by adding nitrogen atoms later, pharmaceutical companies could speed up production and increase the diversity of drugs in their pipeline.
This could also make it easier to scale up drug production globally, helping to address healthcare disparities beyond the economic benefits of this approach. As Sharma notes, health expenditures in the U.S. have been increasing alarmingly, with per capita health expenditures exceeding $12,000 annually. Reducing drug production costs could make healthcare more affordable, not just in the U.S. but also in low- and middle-income countries.
The implications of this research go beyond cost savings. Nitrogen is a key element in biological systems, forming the foundation of DNA, RNA, proteins, and amino acids. By manipulating nitrogen-containing molecules, Sharma’s work could pave the way for novel therapies targeting challenging diseases, including certain cancers and neurological disorders.
Journal Reference:
- Bidhan Ghosh, Prakash Kafle, Rishav Mukherjee et al. Sulfenylnitrene-mediated nitrogen-atom insertion for late-stage skeletal editing of N-heterocycles. Science. DOI: 10.1126/science.adp0974
