Cytotoxic antibiotics leukemia

Haliclonacyclamine F (25), arenosclerin D (26), and arenosclerin E (27) have been recently isolated from the sponge Pachychalina alcaloidifera endemic in Brazil [26]. The alkaloids 25-27 were isolated from the cytotoxic, antibiotic, and antituberculosis MeOH crude extract of P. alcaloidifera by a series of separations on silica-gel and cyanopropyl-bonded silica-gel columns. The structures of compounds 25-27 were established by the same approach employed for the structural elucidation of haliclonacyclamine E (13) and arenosclerins A-C (14-16) [18], as well as by comparison with NMR data for this last series of alkaloids. The alkaloids 25-27 displayed moderate cytotoxic activity against SF295 (human CNS), MDA-MB435 (human breast), HCT8 (colon), and HL60 (leukemia) cancer cell lines. 

Doxorubicin and dannorabicin are antibiotics made from microorganisms of the family Streptomyces peucetius. The stmcture of these anthracyclines contains an aminosaccarhide residue daunozamine attached to a naphthacenequinone nucleus. Doxorubicin differs from daunorubicin in the presence of a hydroxyl gronp at C14. A nnmber of mechanisms have been suggested in which anthracyclines exhibit cytotoxicity. They canse DNA to denature, are involved in oxidation-rednction reactions, chelate bivalent cations and react with cell membranes, changing their fnnction. They are used for severe leukemia, lymphoma, breast and ovarian cancer, and other solid tumors. 

Ansamycin antibiotics are probably the most complex organic compounds produced by the genus Streptomyces. In addition to the antibacterial, they also exhibit antiviral effects. Ansamitocin P-3 shows a potent cytotoxicity against the human solid tumor cell lines A-549 and HT-29. The compound exhibits a significant activity against P-388 lymphocytic leukemia in mice and both 9PS (murine lymphocytic leukemia) and 9KB (human nasopharyngeal carcinoma) in cell culture systems. [38]. 

Gemtuzumab ozogamicin (Mylotarg) consists of a humanized anti-CD33 monoclonal antibody conjugated to the cytotoxic enediyne antibiotic calicheamicin. It has been used to treat a subset of patients with acute myeloid leukemia in association with topotecan -I- cytarabine. Its most common adverse effects are myelosuppression, increased hepatic enzyme activity, infections, fever and chills, bleeding, nausea and vomiting, and dyspnea. 

Okilactomycin was isolated by Imai and associates in 1987 it is an architecturally complex polyketide antitumor antibiotic derived from a bioactive filtrate produced by the actinomycetes, Streptomyces griseoflavus, obtained from a soil sample on the island of Zamami, Okinawa, Japan. (+)-Okilactomycin exhibits significant in vitro cytotoxicity when assayed against a number of human cancer cell lines, including lymphoid leukemia L1210 and leukemia P388... 

Matsuzawa Y, Oki T, Takeuchi T, Umezawa H. Structure-activity relationships of anthracy-clincs relative to cytotoxicity and effects on macromolecular synthesis in L1210 leukemia cells. J Antibiot 1981 34 1596-1607. 

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