Plicamycin Formerly Mithramycin Mithracin

2.4.1 introduction. Plicamycin (16), produced by fermentation of Streptomyces plica-ins and S. argillaceus, was isolated in 1953 (149).It is a member of the aureolic acid family of glycosylated polyketides, which also includes chromomycins, chromocyclomycins, olivomycins, and UCH9. It was subsequently

Interstrand alkylation i = DNA base

Antitumor Natural Products

Figure 3.9. Reductive activation and bisalkylation of DNA by mitomycin C.

Interstrand alkylation dR = Deoxvribose back bone MM = Mitomycin C

Figure 3.10. Interstrand and intrastrand alkylation of DNA by bioreductively activated mitomycin C.

Drugs Attacking DNA

Drugs Attacking DNA

I The "boxed" functional groups can be changed with retention tf significant biological activity. Not all | such changes, however, are successful.

Figure 3.11. Pharmacologically successful modifications of mitomycin C.

found to be identical to mithramycin, a fermentation product of S. argillaceus and S. ta-nashiensis.

2.4.2 Clinical Uses. Plicamycin is highly

Itoxic but is nevertheless administered i.v. for [treatment of testicular tumors (150-153). In lower doses it is used for treatment of hypercalcemia and hypercalciuria associated with advanced cancer, particularly involving Paget's bone disease (154-157).

2.4.3 Contraindications and Side Effects. Severe thrombocytopenia, hemorrhagic tendency, and death can be encountered with the use of plicamycin (158,159). Renal impairment, mutagenicity, and interference with

| fertility are also known to occur with the use of plicamycin. Anorexia, nausea, vomiting, diarrhea and stomatitis, fever, drowsiness,

0 0

Post a comment