Activation of oxygen and mediation of DNA degradation by manganese-bleomycin

Abstract

Many transition-metal compounds have an octahedral cluster of transition-metal atoms as their basic unit. The dusters may be isolated, as in Mo6S8, or condensed at their corners, edges, or faces, depending on the metal to nonmetal

Structural Features Facilitating Tumor Cell Targeting and Internalization by Bleomycin and Its Disaccharide

“…The nature of the enhancement occasioned by the presence of the Cu 2+ and Fe 3+ cations was further defined by studying the effects of the Zn(II) and Mn(III) chelates of BLM–Cy5**. As shown in Figure 5 , both of these cations, which have been shown previously to form stable chelates with bleomycin, 31 , 32 also potentiated the selective binding of BLM–Cy5** to all four cancer cells lines. The observation of enhanced binding/uptake of positively charged species by mammalian cells is well documented, 41 , 42 and not entirely surprising given the negatively charged phospholipids common to the external membranes of eukaryotic cells.…”

“…The results shown in Figures 4 and 5 document that tumor cell binding and uptake are facilitated by four different metal ions, each of which has been shown to form a stable chelate with BLM, and three of which are redox-active and can effect DNA cleavage. 15 , 16 , 30 , 32 The observed effects are clearly different than those obtained in the absence of added metal ions, arguing that each of the metal chelates must survive at least the initial binding event (facilitated by the disaccharide) to the cancer cell surface in order to produce the more efficient tumor cell binding and uptake actually observed. Persistence of the metal complexes following cell uptake might well alter the cellular distribution of the internalized bleomycins as well, potentially leading to enhanced association with the cell mitochondria (cf., Figure 7 a,b).…”

DNA interaction, SOD, peroxidase and nuclease activity studies of iron complex having ligand with carboxamido nitrogen donors

“…Carboxamido nitrogen (N am ) stabilizes higher oxidation states of metal ions and metal complexes having N am donor(s) were found to be important for the activity of nitrile hydratase enzyme [4], metal binding in prion protein [5,6], photolabile nitrosyl complex synthesis [7,8], research in green chemistry [9]. Bleomycin in presence of iron showed nuclease activity [10,11] where carboxamido nitrogen was ligated to metal centre. We have recently communicated the role of carboxamido nitrogen in superoxide scavenging activity as well as nuclease activity for iron and manganese complexes [12][13][14].…”

Copper(II)-based metal affinity chromatography for the isolation of the anticancer agent bleomycin from Streptomyces verticillus culture

“…The ability to coordinate metal ions is a key factor in the mechanism of action of bleomycin which has prompted many studies of its coordination chemistry [12][13][14][15][16][17][18][19][20][21]. The reaction between bleomycin, Fe(II), oxygen and a one-electron reductant in vivo produces activated bleomycin, a low-spin ferric-peroxide species (O 2 2 − -Fe(III)-bleomycin), which initiates DNA cleavage as the first step in its cytotoxic action [18,22,23].…”