Daunorubicin analogs

In other applications, Anne et al. used electrochemical reduction to synthesize new daunorubicin analogs. Kano et al. studied the electrochemical properties of Adriamycin adsorbed on a mercury electrode, while Konse et al. studied the electrochemical properties of Adriamycin adsorbed on pyrolyte graphite electrodes modified by phospholipid membranes. This latter work has relevance to the interaction of Adriamycin with cell membranes. 

The medically useful products demethyltetracycline and doxorubicin (adriamycin) were discovered by simple mutation of the cultures producing tetracycline and daunorubicin (daunomycin), respectively. The tectmique of mutational biosynthesis (mutasynthesis) has been used for the discovery of many new aminoglycoside, macrolide, and anthracycline antibiotics. In this tectmique, a non-producing mutant ( idiotroph ) is isolated and then fed various analogs of the missing moiety. When such a procedure leads to a return of antibiotic activity, it usually is due to the... 

Idarubicin is a semisynthetic anthracycline glycoside analog of daunorubicin and is approved for use in combination with cytarabine for induction therapy of acute myeloid leukemia. When combined with cytarabine, idarubicin appears to be more active than daunorubicin in producing complete remissions and in improving survival in patients with acute myelogenous leukemia. 

Doxorubicin [dox oh ROO bi sin] and daunorubicin [daw noe ROO bi sin] are classified as anthracycline antibiotics. Doxorubicin, often referred to by its trade name adriamycin, is the hydroxylated analog of daunorubicin. Idarubicin, the 4-demethoxy analog of daunorubicin is also available. 

Camptothecin analogs Irinotecan Topotecan Epipodophyllotoxins Etoposide Teniposide Antitumor antibiotics Bleomycin Dactinomycin Daunorubicin Doxorubicin Epirubicin Idarubicin Mitomycin Mitoxantrone Valrubicin Microtubule agents Docetaxel Paclitaxel Vinblastine Vincristine Vinorelbine Enzymes Asparaginase Pegasparaginase Metals... 

A second important and practical improvement is the use of a compound that blocks the efflux of the fluorescent substrate. The measurement of the ratio of fluorescent probe accumulating in the cell with and without a Pgp blocker makes the obtained data less dependent on a number of parameters that may cause variation between cells and samples. We have chosen to use the cyclosporin analog PSC 833 as Pgp inhibitor, which, at a concentration of 2 iM, completely blocks the Pgp-mediated efflux of probes such as daunorubicin or rhodamine 123 in cells with a clinically relevant Pgp content (6,11,14). In addition, we have chosen to measure the practically more convenient cellular accumulation of probe instead of cellular retention after an efflux period, although the latter is theoretically more sensitive (15). In our experience, the use of rhodamine 123 as Pgp probe, combined with PSC 833 as Pgp inhibitor, offers a sensitive and reproducible Pgp functional assay in AML. Although we prefer to use fresh cells, appropriately frozen and thawed cells can be used for this assay, as extensively discussed previously (4,14). 

With the clinical introduction of the 4-demethoxy analog of daunorubicin (idarubicin, Idamycin, Fig. 4-19) in 1991 another set of improvements were achieved. These include higher antileukemic activity, higher potency, and lower cardiotoxicity than the parent compound daunorubicin. The approved indication is acute myelogenous leukemia. 

Daunorubicin, doxorubicin, epirubicin, idarubicin, and mitoxantrone are among the most important antitumor agents. They are derived from the fungus S. peucetius var. caesius. Idarubicin and epirubicin are analogs of the naturally produced anthracyclines, differing only slightly in chemical structure, but having somewhat distinct patterns of clinical activity. Daunorubicin and idarubicin have been used primarily in acute leukemias, whereas doxorubicin... 

Idarubicin is an anthracycUne, which is a DNA-intercalating analog of daunorubicin, which has an inhibitory effect nucleic acid synthesis and interacts with the enzyme topo-isomerase II. 

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