When old drugs get new shape: cisplatin and statin
The incidence of malignant diseases in developed countries is growing. With the surgical removal of tumors and radiotherapy, chemotherapy is still one of the most common treatments. In the largest number of tumors, combinations of two or more drugs (cocktails) are used that target more than one molecule what leads to more successful treatment. In order to further enhance the efficacy of drugs, one of the most recent approaches is the use of so-called “hybrid” molecules. They consist of two covalently linked drugs, which combine the pharmacological characteristics of each drug separately and display even superior synergistic effect.
Statins (such as lovastatin, simvastatin, mevastatin, etc.) are inhibitors of 3-hydroxy-methylglutaryl (HMG) CoA reductase which has been used for the treatment of hypercholesterolemia for years and is one of the most widely used pharmaceuticals in the world. Furthermore, it has been shown that these drugs reduce the risk of heart failure, stroke, and peripheral vascular disease. However, statins also inhibit the synthesis of various metabolites, particularly isoprenoids, which are substrates of post-transcriptional modification of many proteins. These inter-products are important in the various essential cell functions, soin vitro, statins have an antitumor effect on different tumor cells, such as leukemia but also solid tumors, due to antiproliferative and anti-apoptotic activity. To date, it has been established that the combination of statins with antitumor drugs provides an additive effect in prednisone models, showing, in addition to the improved drug action, also the reduced occurrence of undesirable side effects.
The aim of this collaboration is to examine the biological activity of new coordinating compounds based on transition metals (Pt, Ru, Ir, Os). Special emphasis will be on platinum (II) and platinum (IV) compounds with statins as a possible alternative to cocktails. Through this collaboration by creating the compounds that will only become active by entering the cell, the new value to the two existing successful drugs, cisplatin and statin, will be added. The advantage of this strategy in front of others is that certain active substances that will be used in the synthesis are already approved by the FDA for clinical use. The strategy for the synthesis of new, potential will present a remarkable contribution to chemotherapy. The confirmation of the strategy is a recently published study on the antitumor efficacy of a compound formed by the combination of aspirin and cisplatin [Angew. Chem. Int. Ed. 2014, 53, 1963-1967]. The Faculty of Chemistry and Chemical Technology of the University of Ljubljana and IRB concluded in 2001. agreement on joint cooperation. Meanwhile, a long-term collaboration of laboratories in the study of the effects of the newly synthesized compounds resulted in numerous scientific papers and a patent.