Researchers develop a revolutionary process to create anticancer drugs

Dartmouth College research team has developed a new drug discovery and development strategy that can be used to produce targeted therapies for diseases such as cancer and neurodegeneration, according to a study published in Nature Communications.

It is hoped that this process will also be useful for the large scale production of new pharmaceuticals.

The new technique uses a novel synthesis approach for a class of organic compounds called tetracyclic terpenoids. Tetracyclic terpenoids are responsible for more than 100 FDA-approved drugs and are considered to be the highest performing natural product-inspired pharmaceutical class.

"Until now, nothing like this was available for the discovery and development of drugs," said Glenn Micalizio, a chemistry professor at New Hampshire in Dartmouth. "While further developments are expected to strengthen the power of this new technology, I believe we are putting in place a truly enabling and potentially transformative technology for the pharmaceutical sector."

The process combines two new chemical reactions that establish bonds between carbon atoms and a metal-centered cycle formation reaction, also developed by Micalizio.

The new technique brings together molecular building blocks en route to a terpenoid skeleton in just a few chemical transformations. The result is a particularly effective and flexible way to enable drug discovery in this area of ​​medicinal science focused on natural products.

Combined, these reactions allow the exploration of chemically preferred chemical space regions through the direct conversion of inexpensive and commercially available chemicals into high-value and relevant compounds of the point. pharmacy.

The initial work of the research team has already uncovered what could be the most potent and selective modulator of the beta-estrogen receptor, a nuclear hormone receptor that is of great interest to the body. industry as a therapeutic target for many diseases.

"This is an important first step towards the establishment of a new technology platform greatly facilitating the discovery of drugs in a landscape of various therapeutic indications," he said. Micalizio.

To demonstrate the interest of this technique, the study describes the discovery of a molecule selectively toxic to glioblastoma – an aggressive and deadly brain tumor – while showing little effect on cells neural strains and non-cancerous human astrocytes.

"Glioblastomas are incurable and existing therapies have terrible side effects," said Arti Gaur, an assistant professor of neurology at the Geisel School of Medicine in Dartmouth. "It is extremely exciting and encouraging to see that these new compounds can selectively kill brain tumor cells derived from the patient without harming cells from normal, healthy brain tissue."

The team is currently testing in vivo the new therapeutic agent and developing the chemical aspects of the emerging technology platform.

The work is part of an effort to explore and demonstrate the power of advances in organic chemistry to enable the discovery of treatments in a wide range of indications, including neurodegeneration, neuroinflammation and a wide variety of malignant tumors.