Reference

Antitumor effect of adriamycin in comparison with related drugs, and in combination chemotherapy

Antitumor effect of adriamycin in comparison with related drugs, and in combination chemotherapy. Goldin, A.; Johnson, R. K. (Div. Cancer Treat., Natl. Cancer Inst., Bethesda, Md., USA). Adriamycin Rev., EORTC Int. Symp., 2nd, Meeting Date 1974, 37-54. Edited by: Staquet, M. Eur. Press: Ghent, Belg. (English) 1975. CODEN: 35MEAE. DOCUMENT TYPE: Conference CA Section: 1 (Pharmacodynamics) In animals (?) with leukemia L1210, adriamycin (I) [23214-92-8] (13.3 mg/kg) gave a 121% increase in lifespan; intermittant treatment on days 1, 5, and 9 gave a 63% increase in survival time and 1/10 survival rate. The single treatment with I gave better results than daunomycin [20830-81-3], rubidazone [54083-22-6] or carminomycin [39472-31-6], although the latter compds. were effective against leukemia L1210. I was also more effective than the other drugs against leukemia P388. I, daunomycin, and rubadazone were highly effective against B16 melanoma injected i.p. However, s.c. injected B16 melanoma was less responsive to the drugs. All four drugs were effective against Lewis lung carcinoma. In addn., NSC 149584 (adriamycin-14-octanoate) [51898-39-6] was as effective as I against Lewis lung carcinoma. Against leukemia L-1210, increasing the length and complexity of the substituents of I at carbon no. 14 resulted in retention, but no substantial increase in antileukemic activity. With leukemia P388, antileukemic activity was retained with the increase in length and complexity of the carbon 14 substitution, but the antileukemic activity was less than that of I. Substitution of I at carbon 13 of daunomycin failed to result in extensive alteration in activity against leukemias L1210 and P388, although rubidazone was more active than daunomycin. Substitution at the daunosamine amino group of daunomycin resulted in loss of activity against leukemias L1210 and P388. NSC 145971 (daunomycin N-carboxy-.gamma.-lactam) [39024-63-0] was as effective as daunomycin against leukemia L1210. Alteration of the sugar and the aglycone of daunomycin resulted in loss of activity. Two antibiotics, NSC 18334 (cinerubin A) [34044-10-5] and NSC 18335 (cinerubin B) [35906-51-5] showed antitumor activity. The effect of other neoplasm inhibitors on the neoplasm inhibiting activity of I is reviewed; some synergism was obsd.

Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase

Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase. Doroshow, James H. (Dep. Med. Oncol., City of Hope Natl. Med. Cent., Duarte, CA 91010, USA). Cancer Res., 43(10), 4543-51 (English) 1983. CODEN: CNREA8. ISSN: 0008-5472. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The effect of the antibiotics on O radical metab. by cardiac mitochondrial NADH dehydrogenase EC 1.6.99.3 [9079-67-8] was studied. Superoxide [11062-77-4] formation by NADH dehydrogenase after anthracycline treatment appeared to follow satn. kinetics with an apparent Km of 167.3, 73.3, 64.0, or 47.6 mM for doxorubicin [23214-92-8], daunorubicin [20830-81-3], rubidazone [54083-22-6], or aclacinomycin A [57576-44-0], resp. Superoxide formation by NADH dehydrogenase after doxorubicin treatment occurred with a pH optimum of 7.6 and was accompanied by the prodn. of H2O2. Furthermore, drug-related OH radical generation was detected in this enzyme system by the evolution of CH4 from DMSO. OH radical prodn. proceeded only in the presence of superoxide anion, H2O2, and trace amts. of Fe or a chelate of Fe and EDTA and thus was probably the by-product of a transition metal-catalyzed Haber-Weiss reaction.In this experiment, several chemicals are used like 9079-67-8 and 7722-84-1 The antitumor agents mitoxantrone [65271-80-9] and actinomycin D [50-76-0] did not significantly enhance reactive O metab. by NADH dehydrogenase. Apparently, the specific activation of the anthracycline antibiotics to free radicals by NADH dehydrogenase leads to the formation of a variety of reactive O species that may contribute to the mitochondrial toxicity of these drugs. .