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• W1562693843 abstract "Proc Amer Assoc Cancer Res, Volume 47, 20065539 Background: The anticancer anthraquinone mitoxantrone (5,8-dihydroxy-1,4-bis{[2-[(2- hydroxyethyl)amino]ethyl]amino}-9,10-anthracenedione hydrochloride) has been on the market for the treatment of various types of cancer for a number of years. However it never achieved the utility of adriamycin although it has less cardiotoxicity. A variety of analogs were synthesized with two goals one to improve the efficacy profile and two to further reduce the cardiotoxicity. Three of the compounds synthesized and tested were more active than mitoxantrone on a molar concentration basis in the BOT human breast cancer cytotoxicity assay. These were 1,4-bis-{[2-[(2-aminoethylamino-5,8dihydroxyanthraquinone (M-4),1,4-bis-{[2-[(2-hydroxyethylaminoethylamino-6,7-dichloroanthraquinone (M-18), and 1,4-bis-{[2-[(2-aminoethylamino-6,7-dichloroanthraquinone (M-32). (AACR Abstract #3948, 2005) Methods: a variety of anthraquinone derivatives were synthesized and tested. The RIF-1 murine fibrosarcoma tumor model was used to evaluate the antitumor activity of mitoxantrone and mitoxantrone analogs (M-4, M-18 & M-32). Mitoxantrone was tested at 2/3 the published LD50: 4.73 mg/Kg and at 2 subsequently halved doses: 2.37mg/Kg, 1.18mg/Kg. The same doses were used for each analog. Test preparations were administered intraperitoneally (IP) as a single dose in 100 μL, to female C3H mice bearing RIF-1 tumors grown dermally in the flank. Four animals were assigned to each of the treatment groups. Four animals were maintained as untreated controls. Tumors were measured three times weekly for up to 14 days with Vernier calipers. Tumor volume quadrupling time (TVQT), defined as the time required for a tumor to grow to four times (4X) its initial volume (at the time of treatment), was used as a study endpoint. Results: Tumors in untreated control animals quadrupled in size in an average of 6.4 days. Intraperitoneal administration of mitoxantrone extended the mean TVQT to 7.3 days and 7.7 days for doses of 4.73 mg/Kg and 1.18 mg/Kg, respectively. Mitoxantrone analog, M-4 gave a TVQT of 8.6 days at a dose of 1.18 mg/Kg. M-18 and M-32 gave TVQT’s of 8.4 and 7.8 days for respective doses of 4.73 and 2.37 mg/Kg. Summary: mitoxantrone and the mitoxantrone analogs had similar efficacies. At the doses used, M-4 had the best tumor growth delay at the lowest dose (1.18 mg/Kg), M-32 had the best tumor growth delay at the middle dose used (2.37 mg/Kg) and M-18 had the best tumor growth delay at the highest dose used (4.73 mg/Kg). M-32 and mitoxantrone had similar toxicities, as 2 mice with each of these treatments were FDIC (found dead in cage) by day 14." @default.
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• W1562693843 date "2006-04-15" @default.
• W1562693843 modified "2023-09-27" @default.
• W1562693843 title "Cytotoxic anthraquinone compounds revisited II: further pre-clinical testing effect on RIF-1 tumor growth in C3H mice." @default.
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