Daunorubicin determination

The effects of the P-gp inhibitor, GF120918, on the hepatobiliary disposition (biliary excretion) of doxorubicin were determined using a perfused rat liver system (270). Biliary excretion is the rate-limiting process for doxorubicin elimination. In the presence of GF120918, the biliary excretion of doxorubicin and its major metabolite, doxorubicinol, was decreased significantly without alterations in doxorubicin perfusate concentrations or doxombicin and doxorubicinol liver concentrations. In a similar study on the hepatic elimination of other P-gp substrates, including vincristine and daunorubicin, it was reported that canalicular P-gp plays a significant role in the biliary secretion of these compounds (428,429). 

Yang GC, Ha T, Fan E et al (2010) Determination of the absolute configurations of synthetic daunorubicin analogues using vibrational circular dichroism spectroscopy and density functional theory. Chirality 22 734—743... 

The fluorescence distribution of the cells is determined on a flow cytometer for rhodamine 123 in the FL1 channel and for daunorubicin in the FL2 channel. Preferably, identical detector settings are used every day. The blanks are used to position the signal in the first decade. The leukemic blast population is selected based on scatter characteristics. 

A considerable amount of research has gone into elucidating the molecular mechanism of action of these antitumour quinones. While several mechanisms are possible, a single mechanism may not fully explain all of the observed cytotoxic effects. One of the objectives of the NCI and other studies elsewhere has been to determine if there were any structure-activity relationships within the major structural groups ranging from the simplest benzoquinones to the complex multiple heteroatom quinones. One of the main conclusions from these studies was that the most active compounds were mitomycin C, the 3,6-diaziridinylbenzoquinones with 2,5-alkylamino substituents, adriamycin (doxorubicin), daunomycin (daunorubicin) and AZQ (Figure 1). 

The length of the carbon chain at R is determined initially by the polyke-tide starter. In the most important anthracycHnes, daunorubicin and doxorubicin, the ethyl moiety present is oxidized by the cytochrome P450 enzyme DoxA in three steps (Scheme 2). 

The cytotoxicities of these six compounds (Figure 7) were examined in colon cancer cell line SW620 cells. The results in Table II indicated that the aglycon, DNR-A, exhibited 70 to 100-fold lower cytotoxicity than daunorubicin derivatives with various uncommon sugars. This suggests that sugar structure in daunorubicin plays a critical role in determining its anticancer activity. 

Meuter G, Hutchinson CR. Daunorubicin Type il polyketide synthase enzymes DpsA and DpsB determine neither the choice of starter unit nor the cyclization pattern of aromatic polyketides. ] Am Chem Soc 1995 117 5899-5900. 

The self-association of the cytotoxic antibiotics, daunorubicin (X) and doxorubicin (XI) has been studied by Barthelemy-Clavey et al. [76] and Eksborg [77]. The spectral and distribution studies of Eksborg gave constants for the formation of dimers and tetramers of the order of 10" and 10, respectively. It was suggested from the magnitude of these constants that self-association must be taken into account in the determination of distribution ratios of these antibiotics and also in the determinations of their binding to DNA. 

Adriamycin and Daunorubicin - The structure and absolute stereochemistry of daunorubicin (15a daunomycin, rubidomycin) were determined.98... 

Akpofure et al. used HPLC and electrochemical detection at an oxidative potential of 0.65 V to quantify daunorubicin and its metabolites in serum and plasma. Using a different method, Chaney and Baldwin determined Adriamycin concentrations in urine. The determination was performed by adsorption of the compound at a carbon paste electrode and then applying pulse voltammetric analysis at the resulting surface. 

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