Antitumour drug therapy

The anthracycline antibiotic drugs approved for antitumour drug therapy include doxorubicin (adriamycin), epirubicin, daunorubicin, idarubicin, and aclarubicin. These drug substances are structurally similar and characterized by a tetracyclic aglycone linked to amino sugar moieties. Particularly in solutions, the anthracyclines are photolabile. The formation of inactive aglyconesand polymeric substances as a result of the irradiation of anthracycline solutions has been reported. 

Kopf-Maier P, Kopf H. (1994) Metal compounds in cancer therapy oiganometedlic titanium, vanadium, niobium, molybdenum, and rhenium complexes eariy transition meted antitumour drugs. Chapman and HaU, London. 

Take, for example, the hydrophobic drug paclitaxel, a powerful drug employed in antitumour and heart disease therapies. Paclitaxel is not fluorescent, but fluorescent analogues exist toward various life science protocols in which minute quantities suffice. In the amounts required for encapsulafion into thin films and subsequent drug release protocols, they are prohibitively expensive. The next best method is to employ a fluorescent economical mimic of the hydrophobic drug of interest to narrow release formulations that fit the delivery profile desired. Once the formulations are focused, the more laborious HPLC quantitation procedures can be verified with the original dmg of interest. 

Actinomydns were first isolated, in 1940, by Waksman and Woodruff, for their antibacterial action. They roused considerable interest when it was shown that they were very potent antitumour agents. Actinomycin-D completely destroys several types of experimental tumours. In human therapy its effectiveness is only temporary, and its extreme toxidty makes it useless in practice. When DNA and RNA polymerases are tested in vitro on an actinomydn-D-DNA complex as primer, their activity is affected as shown in Figure 4. This inhibiting effect is characterized by the very small amount of drug necessary to completely block the RNA synthesis. Actinomycin-D is a competitive inhibitor of DNA polymerase in a concentration range similar to that of other DNA ligands. 

Canti, G., Lattuada, D., NicoHn, A., Taroni, A., Valentini, G., and Cubeddu, A., Antitumour immunity induced by photodynamic therapy with aluminum phthalocyanine and laser light. Anticancer Drugs, 5, 443,1994. 

---