Against P-388

Biological Activity. The maytansinoids possess antitumor activity, particulady against P 388 lymphocytic leukemia, B 16 melanocarcinoma, and Lewis lung carcinoma. A number of semisynthetic esters of maytansinol have been prepared and exhibit good antileukemic activity (52,255). The maytansides lack antitumor activity, indicating that the ester at C-3 is a requirement for activity (50,52). The carbinolamide also appears to be necessary for... 

The synthesis of the triazinotriazines 519 was achieved (87MI5) by reaction of 3-hydrazino-5,6-diphenyl[l,2,4]triazine 518 with 4-substituted phenacyl halides. These triazinotriazines were screened against P-388 lymphocytic leukemia in mice and were inactive. 

Compounds 594 were screened against P-388 lymphocytic leukemia in mice and were inactive. 

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. 

Morinda parvifolia Bartling Xiao Ye Yang Jiao Teng (root) Methanolic, morindaparvin-a, alizarin-l-methyl ether.50 Against p-388 lymphocytic leukemia growth (in vivo), cytotoxic, antileukemic. 

A new bromopyrrole alkaloid 15 along with racemic 16 was isolated from the Japanese marine sponge Homaxinellct sp. They exhibit weak cytotoxic activity against P-388 lymphocytic leukemia cells with ED50 values of 21.5 pg/ml and 30 pg/ml, respectively [34]. 

Discodermindol (20), a brominated aminoimidazolinylindole, from the sponge Discodermia polydiscus shows IC50 values of 1.8 pg/ml against P-388 (murine leukemia), 4.6 pg/ml against A-549 (human lung), and 12 pg/ml against HT-29 (human colon) [37]. 

The tribrominated bisindole alkaloid dragmacidin (30) from the marine sponge Dragmacidon sp. has antitumor activity against P-388 cells (IC5o 15 pg/ml), A-549 (human lung), HCT-8 (human colon), and MDAMB (human mammary) cancer cell lines (IC501-10 pg/ml) [43]. 

The polyhalogenated monoterpenes 57-59 from the Spanish sea hare Aplysia punctata show identical cytotoxic properties against P-388 mice lymphoma and HT-29 human colon carcinoma (ED50 2.5 pg/ml), A-549 human lung carcinoma and MEL-28 human melanoma cell lines (ED50 1.5 pg/ml) [57]. 

Hiburipyranone (82), a brominated isocoumarine from the sponge Mycale adhaerens collected off Hiburi Island, Japan, is cytotoxic against P-388 cells with an IC50 value of 0.19 pg/ml [72]. 

Secobatzelline A (83) from a sponge of the genus Batzella is active against P-388 (IC50 0.06 pg/ml) and human lung carcinoma A-549 cells (IC50 0.04 pg/ml) [73]. 

Psammaplysin E (84), ceratinamine (85), and molokaiamine (86) from the sponge Pseudoceratina purpurea exhibit potent cytotoxicity against P-388 murine leukemia cells with IC50 values of 2.1, 3.4, and 2.1 pg/ml, respectively [74]. Recently, the related waianaeamines have been isolated from an undescribed verongid sponge from Molokai Island [75]. 

Also 2 -halo-3 -hydroxy derivatives of various anthracyclinones show a high activity against P 388 mouse leukemia in certain in-vivo tests. A compound like 98 has been prepared in the 2-deoxy-2-iodo-a-L-ma no-series by Horton et al. [59, 60] starting from di-O-acetyl-L-rhamnal (28). Similarly, Thiem et al. have also successfully prepared the tetracenomycinone-C glycoside 99 [61]. From 4-0-acetyl-3-0-(p-methoxy)-benzyl-L-fucal (102) the glycoside derivatives 103 and 104 in the talo-series were obtained. 

The N-oxide of indicine (49) exhibits anti-tumour activity in experimental tumour systems, without some of the toxic effects associated with other pyrrolizidine alkaloids. The N-oxides of echinatine and europine show similar anti-tumour activity against P 388 lymphocytic leukaemia tumours.23 Indicine N-oxide is metabolized to the free base in rabbits and humans,62 although the N-oxide is the more active anti-tumour agent. It has been suggested that the conversion of indicine N-oxide into indicine is not essential for its anti-tumour activity.63 Indicine N-oxide is the first pyrrolizidine alkaloid to be tested as an anti-tumour agent in humans. The toxicity and pharmacokinetics of this compound have been studied in 29 patients with advanced cancers.64 The major toxic effect was myelosuppression, but acute liver damage was not observed. 

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]. 

Cleomiscosin A (9) Cytotoxic against P-388 (lymphocytic leukemia) cell line (57)... 

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. ... 

A year later, the crude extracts of Laurencia obtusa, obtained off the coast of Japan, were shown to exhibit a strong cytotoxic activity against P-388 cells. Purification of the crude material and structural elucidation revealed the structure of thyrsiferol 23-acetate (4) [7]. 

Table 1. Cytotoxicity against P-388 cancer ceil line...

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