Anticancer drugs mitomycin

Anticancer drug mitomycin-C Plasma column-switching, extraction column Cl8 and 0.02 M SDS-10% methanol at pH 6.8, analytical column Cl8 and methanol-water 30 70 at pH 6.8 365 nm linearity, 1-400 pg/mL. 38... 

The mitomycins do not react directly with DNA, but require prior activation by reduction of the quinone. This property of bioreductive activation has inspired the design and development of synthetic anticancer drugs that are also activated by reduction, as this is expected to confer a degree of tumor selectivity [45, 46]. Many solid tumors are short of oxygen relative to normal tissue, so reductive activation of the mitomycins and other bioreductive drugs can proceed in tumors, while it is inhibited by the oxidizing environments in normal tissues. 

G. M. Dubowchik, K. Mosure, J. O. Knype, R. A. Firestone, Cathepsin B-Sensitive Dipeptide Prodrugs. 2. Models of Anticancer Drugs Pachtaxel, Mitomycin C and Doxorubicin , Bioorg. Med. Chem. Lett. 1998, 8, 3347-3352. 

Nakamoto, Y., Fujiwara, M., Naguchi, T., Kimura, T., Muranishi, S., and Sezaki, H. (1975) Studies on pharmaceutical modi. cation of anticancer drugs. I. Enhancement of lymphatic transport of mitomycin C by parenteral emulsiofthem. Pharm. Bull., 23 2232-2238. 

Another area in which natural products have had a major impact on longevity and quality of life is in the chemotherapy of cancer (see Chapter 62). In fact, most major anticancer drugs are derived from plants or microorganisms. Important examples include bleomycin, doxorubicin, daunorubicin, vincristine, vinblastine, mitomycin, streptozocin, and most recently, paclitaxel... 

Hartmann JT, Quietzsch D, Daikeler T, Kollmannsberger C, Mayer F, Kanz L, Bokemeyer C. Mitomycin C continuous infusion as salvage chemotherapy in pretreated patients with advanced gastric cancer. Anticancer Drugs 1999 10(8) 729-33. 

Figure 9.17 Release of anticancer drugs from poly(HEMAF-collagen hydrogels. Controlled release of 5-fluorouracil 130), mitomycin C (M, 334), and bleomycin Ml 1,417) into phosphate-buffered water at 37 °C from p(HEMA) polymerized in the presence of drug and 5% eoUagen. The hydrogels were hydrated ( 40% water) throughout the experiment. Adapted from [57].

The in vitro phase II trial of RA-700 employed human tumor clonogenic assay. From the results using a human tumor cell line of lung cancer (PC-6), RA-700 appears to possess time-dependent antitumor activity. The chemosensitivity rate of RA-700 was 67%, 22%, 17% and 10% for ovarian cancer, non-small cell lung cancer, breast cancer and colorectal cancer, respectively. RA-700 showed almost the same chemosensitivity as that of five standard anticancer drugs (adryamycin, mitomycin C, cisplatin, vinbrastine and 5-FU), but the spectrum of RA-700 activity appeared to be different. Furthermore, the antitumor activity of RA-700 had no relationship with prior chemotherapy. These results indicated that RA-700 is a candidate for phase I study [89]. 

Cheung, R.Y. Rauth, A.M. Yu, W.X. In vivo efficacy and toxicity of intratumorally delivered mitomycin C and its combination with doxorubicin using microsphere formulations. Anticancer Drugs 2005,16... 

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]. 

Of the numerous anticancer drugs, eight have been reported to form free radicals, namely doxorubicin (= adriamydn = NSC-123127), daunorubicin (= daunomycin = NSC-83142), mitoxantrone (= NSC-301379), bleomycin (= NSC-125066), neocarzinos-tatin (= NSC-157365), mitomycin C (= NSC-26980), actinomycin D (= NSC-3053), and procarbazine (= NSC-77213). 

Forgfics and Cserh iti [513] studied 21 anticancer drugs with the intention of determining the relative hydrophobicities of these drugs. Retention of these compounds (e.g., vinblastine, paraplatin, doxorubicin, mitomycin C, methotrexate. 

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