HSE Faculty of Chemistry Scientists Discover New Anti-cancer Molecule
A group of Moscow scientists has discovered and explained the activity mechanism of a new anti-cancer molecule — diphenylisoxazole. This molecule has been shown to be effective against human cancer cells. The research, published in the journal Bioorganic & Medicinal Chemistry Letters, makes it possible to produce an affordable cancer treatment drug.
Every cell in our body has a cytoskeleton, a system of microtubules and filaments that support the cell’s rigid shape. Microtubules are formed by the protein tubulin and play a key role in the division of both healthy and tumor cells. Therefore, microtubules are a target for antimitotics — anti-cancer drugs that inhibit tumour growth by disrupting tubulin polymerization. Because the unlimited proliferation of cancer cells is what makes the disease so dangerous, many drugs aim at inhibiting this process.
The tubulin molecule has four binding sites (sites where it can interact with a drug), namely the colchicine, taxane/epothilone, laulimalide and vinca alkaloid binding sites. Several substances are known to bind with tubulin at the colchicine site and ultimately disrupt tubulin polymerization, and all of them contain a trimethoxyphenyl ring.
With the help of computer simulations, the Moscow researchers determined which compounds, including those without a trimethoxyphenyl ring, were able to bind to tubulin, and were able to predict the effectiveness of a new substance for such studies — diphenylisoxazole. This molecule is unique in that it is easily synthesized using available compounds — benzaldehydes, acetophenones, and aryl nitromethanes.
The simulation also showed for the first time that the molecule of a substance needn’t have a trimethoxyphenyl ring in order to bind to tubulin at the colchicine site. All previously known tubulin polymerization inhibitors interacting with the colchicine site had a trimethoxyphenyl substituent in their structure, but this element is absent in diphenylisoxazole. This means that there is a yet unexplored structural class of compounds with antimitotic activity that can be used to create anti-cancer drugs with new properties.
It was later shown that diphenylisoxazole inhibits tubulin polymerization in sea urchin embryos, whose rapid cell division resembles that of cancer, making it a frequent subject of such studies. Adding diphenylisoxazole to a vessel containing fertilized sea urchin eggs inhibited cell-reproduction and caused the embryo to rotate instead of swimming forward. This observation indicates that the substance affected the cells' microtubules. Subsequent experiments proved the molecule's effectiveness not only on sea urchin embryos but also on human cancer cells.
The scientists pointed out that not only the results of the research but also its methodology hold value.
HSE University professor Igor Svitanko, one of the authors of the study
'Previous work by these researchers on the synthesis of drugs against leukaemia and rheumatoid arthritis, as well as on other anti-cancer drugs, has shown the importance of this sequence in designing the scientific experiment — first simulating the structure of the matter with the desired properties, and only then synthesising and testing its biological activity. Posing the question in this way gives only secondary importance to organic synthesis and requires that it take the simplest possible path to the predicted structure. This makes it possible to dramatically reduce the cost of finding and introducing new drugs.’
Professor Svitanko also said that computer modelling makes it possible for young researchers without years of experience and intuition regarding synthetics to participate in such complex studies. HSE University has proposed creating a new computer-modelling laboratory that would synthesize new drugs and other substances using computer predicted structures.
Chemist Polina Yurova works in the same laboratory of the IGIC RAS that she first visited as a tenth grader. In this interview with the Young Scientists of HSE University project, she spoke about the creation of ion-exchange membranes, the ‘hair’ of black holes and her favourite Moscow park.
A joint research team from HSE, Skoltech, MPGU and MISIS has developed a compact sensor for biochemical analysis, opening up a new frontier in the development of the ‘lab-on-a-chip’. Using bovine serum albumin film as an example, the researchers proved that the chip surface can be adapted for selective analysis of multicomponent solutions. Along with enabling accurate blood tests with only 3 to 5 microliters of blood, the chip will help doctors to detect specific disease markers. The study was published in Analytical Chemistry.
A team of Russian scientists, including HSE MIEM researchers, have presented a 3D model of SARS-CoV-2 S-protein transmembrane (TM) domain. Previously, the TM domain had only been believed to anchor the S-protein in its viral membrane without being involved in rearrangement and fusion with the host cell. Yet according to recent studies, the TM domain appears to have a function in the transmission of genetic information, but its role is not yet fully understood. The researchers believe that the model they have created can contribute to a better understanding of viral mechanisms and potentially lead to the development of novel antiviral drugs. The study has been published in the International Journal of Molecular Sciences.
Russian researchers from HSE University and the Russian Academy of Sciences Nesmeyanov Institute of Organoelement Compounds have come up with a new method of enhancing the chemical reaction involved in producing gamma-aminobutyric acid (GABA) analogues used in sedative drugs. Adding fluoride to the catalyst more than doubled the yield of the pure product and increased the total reaction yield by 2.5 times. This approach is expected to make the production of certain drug components more efficient and less costly. The study has been published in the Journal of Organic Chemistry.
In 2023, the first Master's programme 'Chemistry of Molecular Systems and Materials' at the HSE Faculty of Chemistry will enrol students. Half of the study time will be devoted to research projects in the field of modern fundamental and applied research on the topics studied at five institutes of the Russian Academy of Sciences. Dmitrii Roitershtein, Academic Supervisor of the programme and Associate Professor at the Joint Department of Organic Chemistry with the RAS Zelinsky Institute of Organic Chemistry, spoke about the programme to the HSE News Service.
A team of researchers of the HSE Faculty of Chemistry Joint Department of Inorganic Chemistry and Materials Science with the RAS Kurnakov Institute of General and Inorganic Chemistry have designed a novel type of hybrid ion-exchange membrane. Such membranes can be used to produce drinking water from seawater, which is particularly relevant for areas with access to the sea and a shortage of drinking water. The study is published in Desalination.
The HSE University Faculty of Chemistry opened three years ago, and its first intake of undergraduate students is set to graduate in 2023. These students have already demonstrated impressive results in their research—half of second and third-year students have publications in journals indexed in WoS and Scopus, almost a third of which are in Q1 journals. Andrey Yaroslavtsev, Head of the Chemistry programme and Academic of the Russian Academy of Sciences (RAS), told the HSE University News Service about the secret of this success.
The Journal of Alloys and Compounds has published an article coauthored by the Institute of Solid State Chemistry and Mechanochemistry (the Ural Branch of the Russian Academy of Sciences), the Donostia International Physics Centre, and the HSE Tikhonov Moscow Institute of Electronics and Mathematics on the characteristics of cubic double perovskite oxides. To date, experimental measurements of the minerals’ characteristics have not corresponded to the results of theoretical modelling. The work marks the first time that researchers have set themselves the task of explaining this disparity. The data obtained will allow researchers to improve low-temperature fuel cell technologies—one of the main alternatives to current sources of electricity.
Yury Belousov, Associate Professor at the HSE Faculty of Chemistry, joined his colleagues from Moscow State University, Lebedev Physical Institute, and the University of Camerino, Italy, to work on a review, in which they compared and analysed over 200 lanthanide azolecarboxylates. The scholars were the first to systematize the scattered published information in a single source, which will be useful for technology developments in electronics, metallurgy and nuclear medicine, as well as in the chemical and nuclear industries. The review was published in Coordination Chemistry Reviews.
RAS Institute of Problems of Chemical Physics Launches Joint Department with HSE Faculty of Chemistry
The new Department will prepare students for careers in cutting edge research and engineering, as well as entrepreneurial and commercial development. They will be able to promote their own innovative projects and projects developed by their colleagues. The Department is headed by Professor Sergey Aldoshin, full member of Russian Academy of Sciences.