Daunomycin: A New Antibiotic with Antitumor Activity

Abstract

Daunomycin is a new antibiotic isolated from cultures of Streptomyces peucetius. For its physicochemical characteristics it may belong to the group of antibiotics described by Ollis and Sutherland (11). The toxico-pharmacologic studies of Daunomycin administered i.v. to mice and rats indicated an acute LD50 value of 15-20 mg/kg. In the rat daily intravenous administration of 1-1.25 mg/kg for 8-14 days was well tolerated. Daily intravenous injection of 2-2.5 mg/kg for 8 days caused a slight decrease in the number of R.B.C. and W.B.C., but no histological damage was found in duodenal mucosa, testicles and other parenchimas. Daunomycin caused a significant inibition of 10 out of 12 tumors tested. At a daily dose of 1 or 2 mg/kg it had a marked inhibitory effect on ascites tumors (Hepatoma AH 130, Walker carcinoma, Ehrlich carcinoma, sarcoma 180 and O.G.G. myeloma) and remarkably increased the average survival time of the tumor-bearing animals. The antibiotic strongly inhibited also the growth of solid tumors (Ehrlich carcinoma 41.1%, 180 sarcoma 42.2%, Walker carcinoma 66.1%, O.G.G. myeloma 70.8 - 85.2% and MC sarcoma 67.6%). Daunomycin decreased the mitotic index of the Ehrlich ascites tumor and induced mitotic damages of tumor cells.

The Roots of Modern Oncology: From Discovery of New Antitumor Anthracyclines to their Clinical Use

“…Taking advantage of daunomycin's intrinsic fluorescence, it was possible to relate cytotoxicity to strong chromosomal aberrations and nuclear damage as well as to decrease in nucleolar size (23). An important report presented by Prof. Di Marco at the III International Congress of Chemotherapy (July [22][23][24][25][26][27]1963) in Stuttgart, Germany (24), was followed by a seminal paper on February 15, 1964 (25), both showing the efficacy of daunomycin in experimental tumor models. In particular, the second report presented further data on the mechanism of action, evidencing that daunomycin could strongly bind to DNA, interfering with its functions also as a primer in RNA synthesis and in mitosis (25).…”

Quantitative liquid chromatographic analysis of anthracyclines in biological fluids

“…In the early 1960s the first identified anthracyclines, daunorubicin (synonym: daunomycin) and doxorubicin (synonym: adriamycin), were isolated from pigment producing Streptomyces spp [1]. These anthracyclines, together with their semi-synthetic derivatives idarubicin and epirubicin (synonym: epiadriamycin), are by far the most frequently administered in clinical practice today.…”

Biosynthesis of anthracyclines: carminomycin 4-O-methyltransferase, the terminal enzymic step in the formation of daunomycin

“…Although daunomycin (DiMarco et al, 1964), adriamycin (Arcamone et al, 1969), carminomycin (Brazhnikova et al, 1974) and related anthracyclines (Fujiwara & Hoshino, 1983;Strohl et al, 1989;Fig. 1) are important anti-tumour drugs, the biosynthetic pathways for their formation have not been well elucidated (Strohl et al, 1989).…”