Synthesis of the metal anticancer ru-rhein in tumor tissue

recently published in the National Science Review, In the NSR article, researchers at Nanjing Normal University and Nanjing University used the "bio orthosis catalytic lethality" strategy to develop a highly active tumor-targeted metal drug, Ru-rhein, a copper species with high concentrations in tumor tissue that can act as a catalyst to turn non-toxic premeditations Ru-N
and rhein-alkyne into cytotoxic Ru-rhein, Ru-rhein-targeted tumor mitochondrials, and induced autophagy.
the current clinical use of metal anti-cancer drugs targeted, toxic side effects are larger, and long-term use is easy to produce drug resistance. In this work, the researchers, inspired by the concept of "synthetic death" in biology, proposed a strategy of "bio-orthogonally catalyzed lethality", i.e., according to the characteristics of the tumor itself, tumor cells as an anti-cancer drug manufacturing plant, developed a highly active tumor-targeted drug Ru-rheinein, to achieve the cancer cells and tumors in mice with the option of killing and non-toxic side effects of normal cells.
in tumor tissue, copper species have much higher levels than normal tissue. These copper species can act as catalysts for combining two non-toxic drug premedulations, Ru-N
and rhein-alkyne, into the tumor-targeted drug Ru-rhein, with yields of more than 80%. However, in normal tissues, the above reactions are almost non-occurring, so the targeting and selectivity of tumors can be achieved. The researchers tested Ru-rhein's anti-cancer activity in cancer cell line and lotus mice and explored its anti-cancer mechanism. Ru-rhein exhibits high anti-cancer activity in a variety of cancer cell lineages, especially in lung cancer cell line A549, where its anti-cancer activity (IC
value is approximately 5.6 m) is almost equivalent to cisplatin and non-toxic to normal lung cell HLF. Studies have shown that Ru-rhein targets mitochondrials in tumor cells, causing autophagy death in cells through mitochondrial pathways. In mouse models, tumor growth in mice injected with Ru-N
and rhein-alkyne was significantly inhibited compared to the control group, and other organs were virtually unsalted.
this study provides a new way of thinking for drug development for precise and effective treatment of diseases, and finds that BCL strategies are potentially universal and can be extended to other metal anticancer mates, such as OS and Ir's aromatic-based ligations. The study was funded by the National Natural Science Foundation of China. (Source: Science Network)
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