Anticancer antibiotics

The coupling reaction has widespread use in the construction of enediyne systems present in naturally occurring anticancer antibiotics[234]. The Pd-Cul catalyzed coupling reaction of the alkenyl bromides 323 and 326 with the... 

Arcamone F (1981) Doxorubicin anticancer antibiotics. Academic Press, New York... 

Many organic and inorganic compounds, fibers, and particles are capable of damaging nucleic acids by generating reactive oxygen species via the reduction of dioxygen. These stimuli include different classes of organic compounds, classic prooxidants (anticancer antibiotics, various quinones, asbestos fibers, and so on), and even antioxidants, which can be oxidized in the presence of transition metal ions. 

The importance of superoxide-mediated damage to cancer cells was also demonstrated in the experiments with overexpressed mitochondrial MnSOD. Hirose et al. [186] showed that the overexpression of mitochondrial MnSOD enhanced the survival of human melanoma cells exposed to cytokines IL-1 and TNF-a, anticancer antibiotics doxorubicin and mitomycin C, and y-irradiation. Similarly, Motoori et al. [187] found that overexpression of MnSOD reduced the levels of reactive oxygen species in mitochondria, the intracellular production of 4-hydroxy-2-nonenal, and prevented radiation-induced cell death in human hepatocellular... 

Although data presented in the previous section illustrate the diversity of cycloaromatization reactions, most of the following discussion will concentrate on the Bergman cyclization - a reaction that has been studied intensively in recent decades due to its role in the mechanism of biological activity of natural anticancer antibiotics.8,9 We will take advantage of the large body of data produced by this... 

Figure 1-32. Ring-closure reaction of endiyne anticancer antibiotics.

Guanti G, Banfi L, Basso A, Riva R (2005) From natural to rationally designed artificial enedi-ynes towards new anticancer antibiotics activable at will. Chapter 19 in Polyynes Synthesis,... 

Chakrabarti S, Bhattacharyya D, Dasgupta D (2000-2001) Structural basis of DNA recognition by anticancer antibiotics, chromomycin A3 and mithramycin roles of minor groove width and ligand flexibility. Biopolymers 56(2) 85-95... 

A further natural product inhibitor is mithramydn A, a structurally complex anticancer antibiotic. Mithramycin A is a member of a group of aureolic add-type polyketides that are produced by the soil bacterium Streptomyces argillaceus [94]. 

Screening of microbial products has led to the discovery of a number of growth-inhibiting compounds that have proved to be clinically useful in cancer chemotherapy. Many of these antibiotics bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both cause DNA strand scission and interfere with cell replication. All of the anticancer antibiotics now being used in clinical practice are products of various strains of the soil microbe Streptomyces. These include the anthracyclines, bleomycin, and mitomycin. 

Nicolaou KC, Dai W-M (1991) Chemistry and Biology of the Enediyne Anticancer Antibiotics. Angew Chem Int Ed 30 1387... 

Azotomycin is anticancer antibiotic produced by Streptomyces ambofaciens. Total sythesis of it from y-benzyl-N-tert-butyloxycarbonyl-L-glutamic acid (y-OBzi-N-Boc-L-Glu) has been accomplished in nine steps. The mixed carbonic anhydride method was chosen for peptide bond formation. Commerically available y-OBzi-N-Boc-L-Glu was esterified with ethereal diazomethane, deprotected with trifluoroacetic acid-methylene chloride (1 1), and converted to hydrochloride y-benzyl-L-glutamic acid a-methyl ester (y-OBzi-L-Glu-a-OMe HCI) by treatment with dry hydrogen chloride in ethyl ether, MP 129°-135°C (dec.) [a]D25= + 13.3° (CHCI3). 

Because of its excellent tumor-localizing properties, radiolabelling of the anticancer antibiotic bleomycin has long been of interest. Despite its requirement for iron and... 

Figure 4.14 Mechanism of action of neocarzinostatin chromophore 30 Nicolaou, K. C. Dai, W.-M. Chemistry and biology of the enediyne anticancer antibiotics, Angew. Chem. Int. Ed. Engl. 1991, 30, 1387-1416. Copyright Wiley-VCH Verlag GmbH Co. KGaA. Reproduced with permission.

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