Antibiotics mitomycin

The antitumor antibiotic mitomycin C functions by forming cross-links in DNA chains. 

The antibiotic mitomycin C, introduced to give a concentration of 10 jLtg. per ml. in the perfusing blood at the outset, and a continuous infusion of a total of 1 mg. over the course of 4 to 5 hours, was also associated with significant suppression of fibrinogen biosynthesis. The concentrations of mitomycin C used here are at least ten times that which significantly inhibited cellular multiplication in isolated cell cultures. Further studies at lower concentration levels with both puromy-cin and mitomycin C are indicated. 

Shikimic acid (144), or a close relative, has been deduced to be the source of a C7N unit (shown with heavy bonding) common to the antibiotics mitomycin (147)128 129 and rifamycin S (148) 129-131 a similar unit is also apparent in strep-tovaricin D (149). Shikimic acid is a proven precursor for bacterial phenazines which are arguably constructed from two related C7N units132 (for further research on these metabolites, see below). 

In an analogous manner the indole double bond in VIII/203 was opened oxidatively (02, rose Bengal, 200 W halogen lamp, CH3OH/CH2Cl2, 25, 5 h) and the desired eight-membered lactam VIII/204 was isolated in 82% yield [118]. Compound VIII/204 is an intermediate in a synthetic approach to the potent antitumor antibiotic mitomycin A (see Chapter VIII.2). 

The mitomycins are a family of aziridine-containing antibiotics isolated from Streptomyces lavendulae. One of these antibiotics, mitomycin C (MMC), is an antitumor antibiotic frequently used for the treatment of breast, lung, stomach, intestinal, testicular, cholioepithelial, seminal and oral carcinoma [18-20]. When human oral squamous cell carcinoma cell lines (HSC-2, HSC-4) were treated with MMC, the viable cell number was dose-dependently reduced (CC50 of MMC against HSC-2, HSC-3 and HSC-4 cells 3.5, 9.7 and 18 xM, respectively, determined 24 hours after treatment). The rapid decline of polyamines (measured at 3 hours after MMC treatment) was observed prior to the expression of early apoptosis markers such as the production of annexin-positive cells and caspase activation (Table 1) [21]. The interactions... 

Similarly, resistance to the anticancer antibiotic mitomycin in the producing organism, Streptomyces lavendulae, occurs via sequestration of the antibiotic by the binding protein MRD (81, 82). This protein interacts with the mitomycin export system, thus additionally facilitating export of the antibiotic from the cell. The structure of MRD reveals similarity to the bleomycin resistance proteins and, in fact, the protein can also bind bleomycin and confer resistance to this antibiotic (83). 

De Groot A, van der Meyden A. Purpuric allergic drug eruption from intravesicle instillation of the antitumor antibiotic mitomycin C. Dermatosen 1991 39 84-6. 

Aikyiating agents Cispiatin Nitrosoureas Cyciophosphamide Antibiotics Mitomycin C Mithramycin Doxorubicin Antimetaboiites Methotrexate... 

Pyrrolizidine antibiotic mitomycin and related compounds 80YGK1053 79H(13)373,79H(13)411. 

Yet another proposed mechanism of cytotoxio aotion is the generation of cytotoxic free radicals that cause single-strand breaks in DNA. One antibiotic (mitomycin) is capable of alkylating DNA, a mechanism more oommonly associated with the nitrogen mustard antineopiastics but which is entirely predictable from the nuoleophilic aziridine ring found within the struoture of this anticancer agent. 

Some other examples about drug-DNA interactions have been seen in the literature. The antibiotic mitomycin C (MC) and its interactions with DNA were investgated based on guanine oxidation signal by Ozkan et al [78]. Meric et al [53] described a biosensor for the detection of interaction between a compound synthesized as an alkylating anticancer agent and DNA. Jelen et al [79] found a redox active bis-intercalator anticancer drug, Echinomycin, and they showed its interactions with DNA. The intercalator "Adriamycin" and its in situ interaction with DNA was reported by Brett et al [80]. 

There are many alkaloids included in this group that are useful as antibiotics. Mitomycin C is an example of such an alkaloid, and is one of the principally used anticancer antibiotics in Japan as of this writing. Maytan-sine, which was first isolated from higher plants in the Celastraceae, and which was later shown to be produced by microorganisms (e.g., Nocardia sp.), and rifamycin S, which is a material used for the semisynthesis of the antitubercular agent rifampicin, and related alkaloids are also in this category. 

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