(ORDO NEWS) — French scientists have found that the human enzyme HSD17B11 converts chemicals released by sea sponges and their synthetic counterparts into toxic compounds that destroy cells.
The results of the study will become the basis for the creation of new anti-cancer and anti-infective drugs.
Scientists from the University of Toulouse (France) found that a human enzyme converts the chemicals secreted by sea sponges and their synthetic derivatives into compounds that kill cells.
The compounds produced by sea sponges attracted the attention of pharmaceutical companies as early as the 1950s.
Then scientists discovered that one of these substances is effective for the treatment of one of the types of blood cancer.
The compounds were then actively investigated as potential anti-cancer therapies. However, until now it was not known exactly how they destroy living cells.
These compounds, called “lipid alkynylcarbinols”, have a unique structure that combines the properties of alcohol and acetylene on a lipid island.
To learn more about the mechanisms of action of these substances, scientists studied their most effective synthetic derivatives – dialkynylcarbinols, which are a thousand times more active than their natural counterparts.
The researchers analyzed human cells for mutations that make them resistant to the action of dialkynylcarbinols. So the authors found mutations in the gene associated with the HSD17B11 enzyme.
A series of experiments that followed this discovery showed that HSD17B11 converts dialkynylcarbinols into an active form, which then binds to enzymes that remove defective proteins from the cell. Because of this, damaged proteins begin to accumulate in it, and the cell dies.
The scientists then tested the ability of HSD17B11-activated dialkynylcarbinols to kill cells in 15 different types of cancer.
It turned out that the compounds are most effective against cells of a rare type of childhood bone cancer – osteosarcoma. Moreover, cancer cells lacking HSD17B11 survived after treatment with dialkynylcarbinols.
HSD17B11 belongs to the extensive family of short chain dehydrogenase/reductase (SDR) enzymes, which includes over 500,000 proteins found in all living organisms.
Sea sponges secrete alkynylcarbinols to protect against predators, interacting with its SDR, they become toxic and destroy its cells.
To effectively apply the open mechanism, the authors of the work synthesized a number of new chemicals that are activated by other enzymes of the SDR family, and showed that they selectively destroy cells expressing certain SDRs. This technology could form the basis of a new personalized anti-cancer therapy.
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