zinostatin and Leukemia-P388

Polyanionid copolymer of divinyl ether and maleic anhydride (DIVEMA) with narrow molecular weight distribution was synthesized and tested of its antitumor activity. DIVEMA showed a significant antitumor activity against colon 26 adenocarcinoma and FSaI fibrosarcoma transplanted in syngenic mice. Furthermore, DIVEMA was used as a polymeric drug carrier of antitumor drugs to reduce side effects and enhance the antitumor activity of the drugs. Adriamycin and neocarzinostatin were attached covalently to DIVEMA and the polymeric conjugates showed higher antitumor activity than the corresponding mother drugs against P 388 leukemic mice.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Chemical Phenomena; Chemistry; Colonic Neoplasms; Doxorubicin; Drug Carriers; Humans; Leukemia P388; Macromolecular Substances; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Polyelectrolytes; Polymers; Pyran Copolymer; Zinostatin

Zinostatin stimalamer (YM881) is an antitumor agent, chemically synthesized by coupling one molecule of neocarzinostatin (NCS), with 2 molecules of styrene maleic acid half-butylester copolymer. YM881 showed strong cytotoxicity to human (KB, ST4 and others) and mouse (P388, L1210) tumor cell lines and also drug-resistant tumor cell lines. The antitumor effects were observed in murine MM46, colon 26 and other tumor models. The antitumor activity was as effective as NCS or better than NCS at the effective dose ranges.

Topics: Animals; Antineoplastic Agents; Colonic Neoplasms; Drug Screening Assays, Antitumor; Fibrosarcoma; Humans; Leukemia L1210; Leukemia P388; Maleic Anhydrides; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred DBA; Polystyrenes; Stomach Neoplasms; Zinostatin

The novel antitumor antibiotic, trioxacarcin C, was studied for antitumor activities against murine tumor systems. When mice with i.p.-inoculated B16 melanoma were given intraperitoneal injections of trioxacarcin C, the maximal T/C% was 164 by successive administration of 0.125 mg/kg/day (day 1 approximately 10). It also gave the prolongation of life span of mice bearing i.p. P388 leukemia (T/C 141%) by i.p. injection for 10 days, and inhibited the growth of sarcoma 180 (T/C 42%) and Lewis lung carcinoma implanted s.c. (T/C 23%) by i.v. administration for 6 or 7 days. It inhibited the growth of P388 leukemia cells in vitro and showed significant inhibition on the colony formation of HeLa S3 cells. DNA and RNA synthesis were more strongly inhibited than protein synthesis by trioxacarcin C. Also, it induced strand scission of PM-2 DNA without reducing agents or metals. It did not effect the number of white blood cells and blood urea nitrogen value of the peripheral blood.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Bleomycin; DNA Replication; DNA, Viral; Drug Evaluation, Preclinical; Glycosides; HeLa Cells; Humans; Kinetics; Leukemia P388; Mice; Mice, Inbred Strains; Protein Biosynthesis; Transcription, Genetic; Zinostatin