P-388 leukemia cells

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... 

The bisbibenzyls neomarchantins A 133 and B 134, marchantin C, and Glaucescens Bis Bibenzyl A and B possess moderate cytotoxicity against P-388 leukemia cells with IC50 ranging from 8 to 18 pg/mL [123]. Riccardin C and pusilatins B-C display moderate cytotoxicity against KB cells with ED50 of 7.1 to 16.4 pg/mL [79]. 

Brassicolene is a bicyclo[12,l,0]pentadecane also related to cembrane. Discovered in 2000 in the alcyonacean Nephthea brassica, this cytotoxic derivative is the first representative of this new carbon skeleton with a cyclo-propene. Its cytotoxicity in vitro against A-549 Itmg cancer cells and P-388 leukemia cells is, respectively, ED50 3.62 and ED50 0.86p.gml (Duh et al., 2000c). Microclavatin, isolated from Sinularia microclavata of Chinese origin, is another example of a bicyclo[12,l,0]pentadecane, but with a cyclopropane. 

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. 

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],... 

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],... 

Other 2 -fluoro derivatives have been claimed in different patents [63,79] (Scheme 16). Generally, the cytotoxicity of the carminomycin, (4-hydroxy-IDA), and that of the 2 -fluoro derivative against a number of tumor cell lines are equal in vitro. Both compounds show the same activity in vivo in tests against murine P-388 leukemia. Acute toxicity of the fluorine compounds appears to be lower than carminomycin. Carminomycin is another natural glycoside within the family of the anthracyclines. 

Ingenol derivatives, including kansuiphorins A, B, C, and D are found (83, 84). Kansuiphorin A had in vitro IC50 values ranging from 0.03-0.33 pg/mL against various leukemia, melanoma, and non-small cell lung, colon, and renal cancer cell lines, and kansuiphorins A and B were potent against P-388 leukemia in mice with T/C values of >176 and 177% at 0.1 and 0.5 mg/kg, respectively (83). 

Novel nitroxide malonate methanofullerenes (Fig. 1.3), thanks to the presence of nitroxide radicals and fullerene moiety, are able to protect cells from toxic side effects of cyclophosphamide (Gubskaya et al., 2007). Experiments were carried out on mice, in which leukemia P-388 was transplanted. Cyclophosphamide or fullerene individually injected did not increase the average life span of the animals, while the combination of the anticancer drug and nitroxide fullerene derivative resulted in the survival of 70% animals, classifying these compounds as promising modifiers of biological reaction for tumor therapy. 

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