Asplatin against cisplatin-resistant tumors
Two old horses in one team
ChemPort.Ru based on Chemistry World: Aspirin anchor helps cisplatin beat resistance
The binding of cisplatin to the aspirin fragment may contribute to antitumor therapy, which can also cope with those cells that are resistant to the action of cisplatin.
Cisplatin (cis-dichlordiaminoplatin), along with other chemotherapeutic drugs, is used to treat various types of cancers, including testicular cancer, ovarian cancer, lung and rectal tumors. However, the clinical use of cisplatin is limited by the fact that a number of malignant cells may develop resistance to this drug, which has already received such a name as "penicillin for cancer". The mechanisms underlying the emergence of this resistance are known, but so far there are no methods to overcome or reverse it.
Yangzhong Liu and co-authors from the University of Science and Technology of China have received and tested a new anti-cancer drug that may solve the problems of resistance to cisplatin. The new drug – asplatin (asplatin) is a combination of cisplatin and aspirin and is obtained due to the nucleophilic interaction of oxoplatin and acetylsalicylic acid anhydride. The reaction of obtaining a new drug is simple, and the starting materials are relatively inexpensive.
When ingested into the cell , asplatin is restored by the action of ascorbic acid
and it turns into cisplatin and aspirin.
The researchers tested the new drug on a number of human cancer cell lines, including cells resistant to cisplatin, as well as on mice. It has been demonstrated that asplatin demonstrates significant cytotoxicity in relation to malignant cells and acts 10 times more effectively than cisplatin. It was also found that asplatin almost completely overcomes the resistance of cells to the action of cisplatin. When ingested into the cell, asplatin can be reduced by ascorbic acid, which is present in significant amounts in the cytoplasm and intercellular fluid. The restoration of asplatin activates the prodrug and leads to the formation of cisplatin and aspirin in the cells.
It is known that the cause of resistance to cisplatin is a number of adaptive mechanisms of the cell, including reduced absorption of the drug by the cell, deactivation of the drug, tolerance of DNA to the drug and more effective DNA repair. Doping cisplatin with aspirin changes the way the cell absorbs both the platinum-containing drug and aspirin. The results obtained by Liu suggest that more asplatin than cisplatin enters the cell, while the degree of DNA metallization increases – perhaps these circumstances contribute to overcoming resistance. Another possible explanation for the greater efficacy of the new drug is that the simultaneous release of cisplatin and aspirin alters the cell's response to DNA damage caused by cisplatin.
As Dan Gibson, a specialist in medical and bio–organic chemistry from the Hebrew University of Jerusalem (Israel) notes, the new work demonstrates the advantages of using platinum(IV)-based prodrugs with bioaxial ligands (in this case, aspirin) and increasing the effectiveness of cisplatin in vivo. He adds that this method of targeted drug delivery could be a breakthrough in cancer chemotherapy.
Article by Qinqin Cheng et al. The Ligation of Aspirin to Cisplatin Demonstrates a Significantly Synergistic Effect to Tumor Cells is published in the journal Chemical Communications.
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