Research findings anticipated to facilitate production of novel drug candidates

Pharmaceuticals commonly available on the market are developed by linking together rings of molecules to generate drugs that treat conditions like depression, pain, and leukemia.

David Nagib. Image Credit: Kiyotaka Nagaki

However, generating the rings and developing them in a way that suits each disease is a difficult and costly process in medicinal chemistry.

However, recent research puts forth a way to explicate that transformation. According to the researchers, the observation would make it effortless to create novel drug candidates. The study was published on November 16^th, 2021, in the Chem journal.

David Nagib, a senior author of the study and associate professor of chemistry at the Ohio State University, compared the chain of molecules to a belt with no holes. As there is no means to secure the circle and no measurements for the placement of the holes, the belt cannot be assembled so that it is kept closed.

The problem we were trying to solve is how do you punch the hole so that it fits you perfectly, and get it right on the first try without measuring. The trick here was we had to put the holes in just the right place, but we had to figure out precisely where the holes should go, without any markings to tell us where that might be.”

David Nagib, Study Senior Author and Associate Professor, Chemistry, Ohio State University

The “belt” in this context refers to the string of carbon-hydrogen bonds, the most prevalent bonds in both nature and medicines. The majority of the drugs have rings of carbon-hydrogen bonds bound together by a “bridging” nitrogen atom, inside the complex structures that interact accurately with cellular components in the body—similar to a key fitting into a lock.

The frequently found ring in all medications is six-sided ones, known as piperidine.

However, piperidines are hard and costly to produce, majorly because chemists cannot rapidly or cheaply inexpensively replace a carbon-hydrogen bond with other chemical bonds.

Scientists from Nagib’s laboratory at the Ohio State identified a means to replace that bond—by creating a “hole” that enabled them to close the belt—by oxidizing two carbon-hydrogen bonds.

This enabled them to choose hydrogen molecules and eliminate them from the molecule chain. The researchers later employed light and a copper catalyst to convert one of those bonds into the required nitrogen ring. The light excited the catalysts in a chain mechanism same as photosynthesis—how plants utilize light to prepare their food.

The mechanism resolves an issue for producing early-stage drug candidates still in development—which is still high-priced to be utilized to mass-produce medication. Nagib states that future research would concentrate on using a less expensive starting material to enhance production.

This discovery is something that can make it possible to more rapidly create a library of drug candidates for testing, so you can identify the right, most potent, most effective one more quickly.”

David Nagib, Study Senior Author and Associate Professor, Chemistry, Ohio State University