New cancer therapy Natural anti-cancer drug replicated

New promising approach to developing effective cancer medicines
Often, the key to treating previously incurable diseases is in nature. For example, for a new, promising cancer drug, the scientists of the German Cancer Research Center (DKFZ) have successfully successfully synthesized synthetic. The DKFZ experts have succeeded in "reproducing the three-dimensional structure of the promising anti-cancer drug fumagillin," according to the DKFZ. In cell cultures, the synthetic substance has proven to be an effective remedy for cancer cells and has been significantly more stable than the natural product.

According to the DKFZ, the synthetically produced substance could serve as a starting material for the development of anti-cancer and anti-obesity medicines. According to the researchers, natural fumagillin is formed by the so-called "watering can mold" (Aspergillus), and more than 20 years ago American researchers discovered by chance that fumagillin inhibits the growth of cancer cells. It was also found in the experiments that treated animals lost a lot of weight, suggesting a use of the mushroom drug against obesity. However, the promising substance has shown significant weaknesses in preclinical trials. "It proved too unstable and caused severe side effects in the central nervous system," says the DKFZ.

Natural products are the basis for many important medicines
"Many important drugs, especially antibiotics and cancer drugs, are based on natural products," says Aubry Miller, who heads the drug discovery research group at DKFZ together with his colleague Nikolas Gunkel. In general, however, "the original substances must still be chemically optimized to improve their action and their pharmacological properties." For this, the natural products are usually modified by chemists. For example, the active ingredient beloranib was thus produced. This "modified" fumagillin causes fewer side effects, but remains as unstable as the natural starting substance, reports the DKFZ.

Structure of the fungus substance replicated
In their investigations, the DKFZ scientists, together with colleagues from the Institute of Pharmacy and Molecular Biotechnology of the University of Heidelberg, opted for a different approach. They did not develop synthetic fumagillin, but synthesized a molecule that mimics the three-dimensional structure of the substance without being chemically related to the fungal substance, explains the DKFZ. Fumagillin works by blocking a specific enzyme in the cells and "our goal was to tailor the synthetic model as closely as possible to the structure of fumagillin so that it has similar biological properties to the natural substance," explains the lead author of the current study , Michael morning. Using crystal structure analysis, researchers were able to see that their simplified molecule binds to exactly the same amino acids in the active site of the enzyme as its natural counterpart.

Growth inhibited by tumor cells
According to the DKFZ, the new drug actually inhibits the growth of blood vessel cells and of tumor cells. Although the effect was somewhat behind the natural product, the substance was clearly superior to the natural original in terms of stability. "There are still many biological tests out. For example, we do not know anything about the side effects in the central nervous system, "explains Aubry Miller. But the researchers see in their molecule a "starting material that can be further optimized." The potential of the substance is enormous in view of its interesting effect against many tumors and obesity and should urgently be further explored, according to the experts. (Fp)