MOSCOW, April 17A team of NCFU scientists as part of an international research team managed to obtain more bioavailable and less toxic substances with high anticancer activity. The resulting compounds have been tested for activity against the most aggressive forms of cancer, which are not treatable by most known drugs. The results are presented in Bioorganic & Medicinal Chemistry Letters.
According to the International Agency for Research on Cancer (the WHO agency that deals with cancer), there were 20 million new cases of cancer worldwide in 2022, but this figure is projected to increase by 2050. 77% and will reach 35 million
As explained at the North Caucasus Federal University (NCFU), today in clinical practice, to treat aggressive and advanced forms of cancer, they use compounds that are very toxic and leave cell breakdown products in the body, which is unacceptable in the case of brain tumors. Therefore, it is important to look for new drugs that will not destroy, but deactivate cancer cells.
According to experts, the only substance widely used in practice with such activity is retinoic acid (used to treat brain tumors ), however, resistance to it quickly develops, which leads to extremely serious consequences.
A team of NCFU scientists together with colleagues from Texas State University presented three classes of compounds — 2-aryl-2-(3-indolyl) hydroxamic acids, which, according to the researchers, have, according to the researchers, «the unique ability to convert cancer cells into healthy human tissue.» However, during their work, scientists encountered the problem of poor bioavailability of these compounds; they were cleared from the blood too quickly.
“Using chemical modification, we managed to “tweak” the molecule so that it did not have a fragment vulnerable to the effects of blood components,” said Alexander Aksenov, co-author of the scientific publication, dean of the NCFU Faculty of Chemistry.
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In particular, according to him, two types of analogues of hydroxamic acids have been synthesized — acetamides and oxazolines, which do not contain this fragment, but do not lose the effectiveness of the “protected” compound.
Moreover, as the scientist claims , relative to some tumor tissues, the effectiveness even increases; for example, a number of acetamides showed even higher biological activity against neuroblastoma and colon adenocarcinoma. In addition, the authors of the study proved that the resulting compounds were 700–1500 times less toxic to healthy cells.
“The compounds we obtained can transform cancer cells into healthy ones, causing re-differentiation, which is fundamentally different from the drugs currently used in clinical practice,” the dean explained, adding that the development of this technology will make it possible to effectively treat both the most dangerous forms of cancer, located in the brain, as well as other types of tumors.
In his opinion, in the future, treatment of cancer patients is likely to have significantly less consequences for the body, and the development of differentiating agents will make it possible to carry out therapy without surgery, similar to severe bacterial infections .
“In the future, our team will continue to search for new, more effective molecular structures, since the specificity of oncological diseases requires an individual selection of a cocktail for each patient,” the scientist emphasized.
The research was supported by the Russian Science Foundation.
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