A group of researchers investigate a promising molecule for new drugs

Uncontrolled use of antibiotics in recent decades has led to the development of a huge number of resistant bacteria. In other words, humanity may face a challenge when antibiotics stop working. To avoid ending up in the ‘new Middle Ages’, a set of measures is needed, including the development of a new generation of drugs. This path may take years, but it is important to make the first step towards the goal.

The first step towards studying a promising molecule that could become the basis for new drugs in the future is the project ‘Next-Generation Antibiotics Targeting Gram-Negative Pathogens’. The project was successful in the ‘NWO Hop-On Call for Researchers Based in Ukraine: NWO-NRFU Partnership Initiative 2023’.

We asked the author of the Ukrainian part of the project, Dmytro Volochnyuk, Head of the Department of Medicinal Chemistry at the Institute of Organic Chemistry of the NAS of Ukraine, Professor of the Department of Supramolecular Chemistry at the Institute of High Technologies of Taras Shevchenko National University of Kyiv: what molecule is he researching and what result does he want to achieve?

“Recently, a ‘Hit’ molecule was found in one of the European ‘libraries’ of compounds. What kind of compound it is is still a mystery, I will tell you more after the project is completed and the article is published”, Mr. Volochnyuk said. “According to preliminary data, the new molecule can compete with preclinical compounds from the world’s best pharmaceutical companies!”

As part of the project, researchers will make sure that the molecule is really promising and can be modified.

According to the researcher, the new compound has so-called chiral centers. These centers are the same in the order of atomic connection but differ like mirror reflections. One of them can be useful, and the other can be harmful.

“We will check whether the molecule ‘works’ and how it interacts with pathogenic bacteria”, the PI says. “Then, during the second phase of the project, we will try to synthesize chiral analogs of the compound and find more active molecules”.

Bringing the compound to preclinical trials requires a lot of hard work.

“Large pharmaceutical companies strive to develop medicines that patients need every day – for heart, neurodegenerative and oncological diseases”, Dmytro Volochnyuk explained. “The cost of developing any new drug is huge.  And, unfortunately, antibiotics are not very interesting for these companies”.

That is why it is important to involve the academic community in the development of innovative antibacterial agents. With the help of grant funding researchers can perform ‘initial’ research to discover new mechanisms to fight pathogens.  “In addition, the results of this research can be published”, the PI emphasized. “This is hardly ever possible in other commercial projects”.

In order to take part in the call, Ukrainian researchers had to find partners from the Netherlands whose projects are already funded by the NWO. Was it difficult to find such partners?

“My Dutch colleagues found me”, the PI smiles. “We have been cooperating with Leiden University for a long time, and one of my students has recently entered Nathaniel Martin’s PhD program. Dr. Martin is the PI of the project I joined. The research world is very small”.

The project, led by researchers from the Netherlands, develops a methodology for biochemical screening of the pathogenic bacteria behavior in the presence of external chemical molecules. The group welcomed the Ukrainian researcher, as Dmytro Volochnyuk has extensive experience in chemical services in the early stages of drugs development. Besides, he has long been cooperating with Enamine Ltd and UkrOrgSynthesis Ltd (UORSY) and can use state-of-the-art equipment of these companies for research.

“I am grateful to the NRFU for the opportunity to join the Dutch researchers’ project”, Prof. Volochnyuk added. “The Dutch group is very professional. This is one of the best groups in Europe that conducts research on the border of modern biology and chemistry. Without this funding, our research would have to be postponed until better times…”.

The results the researchers plan to obtain can be developed in subsequent projects. In particular, the researchers are already examining Horizon Europe calls, where research aimed at creating new drugs receive very considerable funding.

Interviewed by Svitlana Galata