Dmitry Obydennov: "We Will Learn to Cope with All Diseases"

13:43, November 1, 2021

Organic chemist talks about fighting viruses, renewable fuel, and cancer treatment

It's My City portal together with Brusnika company launched a special project about Ural scientists. This time, the "Science in the City" column features an interview with Dmitry Obydennov, associate professor at the Department of Organic Chemistry and High-Molecular Compounds at UrFU. His research brings new medicines and steps towards using recycled resources and reducing harmful emissions. We tell what his work consists of, what problems scientists face in Russia and whether cures will be found for cancer and other dangerous diseases.

Science

Organic chemistry fascinated me with its diversity: you can approach it from the perspective of physics, studying luminescence, and from the perspective of biology, working on biochemical transformations. When I was at school there were 15 million registered organic compounds, at university we were told that there were already 25 million, and recently the figure grew to almost 150 million. This is not just a sporting interest of scientists, but it is the development of medicine, industry and organic electronics, such as modern solar cells or organic LEDs that are in telephones.

Work in Germany and Russia- In 2012 I defended my PhD thesis and with a grant from the German Chemical Society went for an internship in Germany. Working there opened my eyes to many things. I learned about European approaches, felt the importance of publications in scientific journals, tried my hand at operating a very expensive NMR spectrometer [a device for determining the order in which atoms combine into molecules - Ed. note] and was surprised at how quickly the reagents for work in Germany are delivered.

In Russia, imported reagents have always been difficult to come by. Recently, most often they are provided by Sigma-Aldrich, which can bring reagents within four months. This is still fast; a few years ago, some reagents took years to arrive, and it was easier to synthesize them yourself than to wait. In Germany, you could get the necessary materials almost the next day, so the transition from idea to implementation there requires a much shorter period of time.

I adjusted to our system and am no longer afraid of bureaucracy: I order reagents ahead of time, thinking about the work for months in advance. This is very disciplined, because on average, each publication takes from one to two years, and in some cases even a decade.

Green Chemistry and Viagra

Today in our laboratory we are involved in several areas. One is related to the study of physical properties of compounds (we, for example, grow crystals that resemble gemstones). Another is the bioactivity of substances, which may be of interest in pharmacology. The third is with the so-called green chemistry. The last direction appeared in the 1990s and is associated with the concern of the current generation about the future: to reduce emissions of harmful substances, the search for alternative fuels and sources (i.e. recycling of renewable resources) and increase the efficiency of chemical processes.

By the way, the production of Viagra, one of the most commercially successful chemical products in the world, was optimized using the methods of "green" chemistry by the American pharmaceutical company Pfizer. Previously, tons of solvent were used to synthesize the compound. Today, that volume has been reduced to a few kilograms, which allows for lower costs to obtain the same amount of the drug. It's both more profitable and more environmentally friendly.

In our laboratory, we are also constantly trying to regenerate the solvents we use and search for convenient reaction conditions, although not on an industrial scale.

"Our research is like playing with a construction set"

Right now in the laboratory we are doing organic synthesis, which, figuratively speaking, reminds us of playing with a construction set. Only usually you build houses or cars out of cubes, but in organic chemistry, you build new molecules of a more complex structure out of molecules. It is important for us not just to stack "molecular bricks" on top of each other, but also to invent new "parts" and connect them to each other in previously unknown ways. Not only physical properties (melting point, color), but also biological properties (smell and effect on the body) depend on the order in which the molecule is "assembled" (i.e. its structure).

In the laboratory, we mostly work with heterocyclic compounds - substances that many people encounter almost daily. For example, the smell of freshly baked bread or cotton candy is so recognizable just because of one such compound - maltol. It is also used as a food additive E636 to give a fruity smell. Where does maltol come from? Glucose, for example, which is found in bread, loses water when baked and turns into a more stable substance, maltol.

In order to find new medicinal molecules based on heterocyclic compounds, we need to test thousands of compounds. And such molecules are used, for example, to create HIV-integrase inhibitors. These are substances that prevent the reproduction of the immunodeficiency virus in human cells. The fact is that the virus has enzymes that are catalysts of biochemical processes - special proteins through which the virus affects the body. Inhibitors firmly bind to these proteins and turn off the catalytic reaction, thus suppressing the virus reproduction.

"We are not competing with pharmaceutical companies"

The path from a new compound to a dosage form is very complicated, long, and expensive, costing several billion dollars. I can't imagine how this path can be taken in a university setting. So we don't compete with European, Chinese, American, or Japanese pharmaceutical companies in our work. What matters to us is scientific novelty and fundamental interest. Our methods go beyond the walls of the laboratory in the form of scientific publications. Some of the compounds that are available to scientists thanks to our work are included in catalogs and are actively used by pharmaceutical companies to discover new drug compounds.

To find the optimal structure of a drug substance, specialists add different fragments, conduct experiments, and watch how living organisms react to the drugs. It's a lot of work. Thousands of different compounds have to be tested first on cell cultures, then on animals - mice, monkeys - and only after that, if all is well, on humans.

Yes, sometimes we can see from the very beginning that a compound is active and may have medical prospects. But what kind - it's hard to predict. Biologists at the Institute of Natural Sciences at Ural Federal University study the cytotoxic properties of the compounds we synthesize, checking whether the substances have anticancer activity. Sometimes they do, but it happens that they are more than happy to kill not only cancerous cells, but also healthy cells.

"I believe we can learn to cope with all diseases"

Given the high rate of development of organic and medicinal chemistry, I think that sooner or later we will have very effective drugs not only to fight viruses, but also cancer and other socially significant diseases.

Previously, in order to carry out antiretroviral therapy, a patient had to take a lot of drugs, which affected both the kidneys and the liver. Now one pill a month is enough. This is not only a serious level of medicine, but also the highest level of organic chemistry. So I believe that we will learn to cope with all known diseases.

Admittedly, there is a possibility that new threats will emerge by then. But looking at the students we teach, people who are passionate, knowledgeable, and interested in what's going on in the world, I think organic chemistry will also cope with the new challenges.