Freedom to the defender of the genome!
Biologists from Russia have learned to turn on "DNA repair" in cancer cells
Scientists from A drug has been created in St. Petersburg that forcibly forces cancer cells to start repairing their DNA and self-destruct when the genome is fatally damaged, according to articles published in the journals Chirality and Bioorganic & Medicinal Chemistry Letters.
"We have completed experiments with a new class of p53 protein activators. The activity of the compounds we have created is noticeably higher than that of the most powerful drugs developed in the advanced scientific centers of the USA and Europe. Medicines based on them can become a new step towards the creation of effective and safe means for chemotherapy," said Alexander Garabagiu, professor at the St. Petersburg State Institute of Technology, whose words are quoted by the press service of the RNF. A significant part of cancerous tumors in humans and other animals occurs due to a breakdown in the p53 gene. It is responsible for protein synthesis, which monitors the integrity of genetic information and includes a self–destruction mechanism – apoptosis - in case of serious breakdowns. Therefore, cell cultures with a damaged p53 gene are extremely difficult to destroy due to the lack of a "self-destruction program" in their genome.
In some cases, cancer cells have a full-fledged version of the "guardian of the genome", but it does not work due to the increased activity of another protein, MDM2. It neutralizes p53 molecules in healthy cells and prevents them from starting the process of DNA repair or self-destruction at a time when it is not required.
In recent years, as Garabagiu and his colleagues tell us, domestic and foreign scientists have been actively trying to create or find a molecule in nature that would neutralize MDM2 and help the cell more actively fight small mutations and larger breakdowns in DNA. Most of them have serious side effects and low effectiveness.
Russian molecular biologists and chemists were able to solve this problem – they studied the structure of MDM2 and found several weak points in it. Using this knowledge, they changed the structure of several aromatic hydrocarbon molecules that can combine with this protein and neutralize it.
Having received several new versions of such "activators" of DNA repair systems, the scientists tested their work on cell cultures extracted from malignant tumors in the rectum and in human bones. These experiments showed that the compounds created by Russian researchers blocked MDM2 and included p53 much more successfully than their "competitors", killing about 40% of cancer cells.
Figure from the article Grigoreva et al. Proapoptotic modification of substituted isoindolinones as MDM2-p53 inhibitors (Bioorganic & Medicinal Chemistry Letters, 2017) – VM.
The successful completion of these experiments, according to scientists, opens the way for clinical trials and the subsequent use of such molecules in medical practice.
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