Leukemias P 388

The trienomycins ate isolated from Streptomjces sp. 83-16 (43,44). The assigned stmctures (Fig. 12) were based on spectral data. Acid hydrolysis of trienomycin A yielded D-alanine (42,44). The trienomycins have no antimicrobial activity but have good antitumor activity. Trienomycin A is the most active, exhibiting good in vivo antitumor activity against sarcoma 180 and P 388 leukemia in mice (241). 

Haliclona tulearensis in 1999. In this paper, it was also reported that halit-ulin exhibited significant cytotoxicity against P-388 (leukemia), A-549 (lung), HT-29 (colon) and MEL-28 (melanoma) tumor cell lines. 

Allamanda cathatica L. Yuan Xi Huang San (whole plant) All amandin.33 Treat P-388 leukemia. 

Cytotoxic and antifungal pyrroloquinoline alkaloids have been isolated from the Caribbean deep water sponge Batzella sp. Isobatzelline A (166) is considerably more active than the halogen-free isobatzelline B (P-388 leukemia IC50 0.42 and 2.6 pg/ml, Candida albicans IC50 3.1 and 25 pg/ml, respectively) [127]. 

Thus, the development of new anthracycline antibiotics is of interest in which the therapeutical width is enhanced by decreasing toxicity and increasing specificity. Several screening methods are presently available in clinical tests. One is carried out by measurement of the survival rate of mice, induced with P 388 leukemia carcinoma [30, 32], Other methods are based on in-vitro tests either the 50% inhibitory concentration (IC50) of nucleosomal RNA synthesis is measured or the growth of tumor cell cultures like He La is observed [34],... 

In the recent time, a great interest was aroused for platinum IV compounds. The scientists-organochemists of the Institute of Theoretical Problems of Chemical Physics synthesized complexes of platinum IV with aminonitroxyl radicals. These compoimds were tested on the experimental model of P-388 leukemia. In the experiments, the complexes exhibited a strong effect on mice-leukemia-carriers sometimes to complete recovery the toxicity reduced two- to four-fold [70]. 

The most impressive results were obtained for low doses of cisplatinum and complexes of platinum IV with amino nitroxyl radicals applied in combination for treatment of P-388 leukemia. The survival rate for leukemia mice was 100%. As was noted above, nitroxylation of antitnmor componnds was successful. There are some other examples of application of hybrid compounds containing nitroxyl radicals in their molecules. 

Platinum(II) complexes have antitumor activity, and have been tested against P-388 leukemia (derivatives of the substituted o-phenilenediamine). Their antitumor activity has been connected with many factors. These include the formation of chelate rings and their strength, the nature and the influence of different substituting groups, and the relative stability of the Pt(II) complexes. ... 

Kikuchi, M., Uekama, K. Enhancement of antimmor activity of carmofur (HCFU) by dimethyl-p-cyclodextrin complexation in P-388 leukemia-bearing mice. Xenobiotic Metab. Dispos. 1988, 3, 267-273. 

Most recently, Japanese researchers have isolated and characterized a number of new compounds from C. harringtonia var. drupacea these are listed in Table II along with their activities against P-388 leukemia cells. For comparison, the activities of the established active compounds harringtonine (2), homoharringtonine (3), deoxyharringtonine (4), and isoharringtonine (7) are also shown. 

Compound Biological Activity in P-388 Leukemia Cells ICso (/ig/ml) Ref. 

Wang et al. (97) have synthesized the cephalotaxine esters 329-342. Their cytotoxic activities against P-388 leukemia cells are shown in Table VI. Note that the antileukemic activities of compounds 329,2 /I-330,2 /f-330 -t- 2 5-330,2 li-332, and 333 are comparable to that of homoharringtonine (3), and four others TR-231,2 S-331,340, and 341) show moderate activity. The activity of homoharringtonine (3) is shown for comparison. 

Growth Inhibition (%) of Cephalotaxine Esters against P-388 Leukemia Cells In Vitro... 

Aloe emodin was shown to possess activity against P-388 leukemia in mice although a previous study showed that aloe emodin did not inhibit L-1210 leukemia (Kupchan and Karim, 1976). The National Cancer Institute tested aloe as an antineoplastic, with negative results (Hecht, 1981). 

Table 2. In vivo cytotoxicity of Ecteinascidins and Eudistomin K against P-388 leukemia, B-16 melanoma, Lewis Lung carcinoma xenograft (LL), M5076 ovarian sarcoma and MX-1 human mammary carcinoma xenograft, doses in pg/kg/day. ...

Bioassay-guided fractionation of an alcoholic extract of B. megapotamica, which showed significant activity in vivo against P-388 leukemia in mice and in vitro against cells derived from human carcinoma of the nasopharynx, yielded four potent antileukemic trichothecenes baccharin, Fig. (57), baccharinol, Fig. (58), isobaccharinol, Fig. (59) and isobaccharin, Fig. (60) [84],... 

It should be noted that while these compounds show potent in vivo antileukemic activity against P-388 leukemia in mice, very similar compounds, e g., roridin D, Fig. (61) show no in vivo activity. The key difference seems to be the presence of an oxygen substituent in the ring A of the trichothecene nucleus in the baccharinoids. More recently, screening of plants from South America for antineoplastic activity and subsequent assay-guided fractionation resulted in the isolation of several pentacyclic triterpenoids as active constituents from some Baccharis spp [85],... 

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