Against leukemia cells

The pyrrolonaphthyridines 208 and 209 can be prepared from rearrangement of the pentacycle 207 upon treatment with trifluoroacetic acid (TFA) (Scheme 52). These products are of interest as they have the same structural skeleton as the indole alkaloid (—)-goniomitine, isolated from the root bark of Gonioma Malagasy <1995JOC3282>. Compound 208 has since been used in the synthesis of further derivatives which show cytotoxic activity against leukemia cells <2001BML79>. 

Raltitrexed <1998MI423> can be used in the treatment of advanced colorectal cancer. Substituted 2-thienyl-1,8-naphthyridin-4-ones 25 < 1999JME4081 > exhibit cyctotoxicity and inhibit tubulin polymerization. Cyclopentathiophenes, for example, 26-29 <2002BMC2185>, have been successfully used against leukemia cell lines. 

Fig. 5 Effect of treatment type on the increase in tumor volume in mice inoculated with BLSC-KU cells. The animals in treatment groups received i.v. doses of doxorubicin via tumor-specific or non-specific liposomes on day 0, 3, and 7 after the initiation of treatment. The tumor-specific and non-specific liposomes were conjugated with MoAbs against leukemia cells and normal mouse IgG, respectively. (Adapted in part from Ref. l)...

Likewise, no evidence for obvious synergy was found between tributyltin (50 nM) and 3,3, 4,4, 5-pentaCB (100 nM) or Aroclor 1016 (50 ppm) in inhibiting human natural killer cell in vitro lytic actions against leukemia cells (Whalen et al. 1998) or among methylmercury (0.1-2 pg/mL), a CDD/CDF mixture of 2,3,7,8-tetrachlorodibenzo-/ -dioxin, 1,2,3,7,8-pentachlorodibenzo-p-dioxin,... 

Imbricatine. C24H26N4O7S, Mr 514.55, a benzyl(tet-rahydro)isoquinoline and imidazole alkaloid from the starfish Dermasterias imbricata. I. is as yet the only alkaloid of this class that does not originate from a plant source. I. induces an escape reaction in the sea anemone Stomphia coccinea when it comes into contact with the starfish. I. has cytotoxic activity against leukemia cell lines. 

Bogert and Hand used 2-aminobenzonitrile derivatives to generate 2-styrylquinazoline-4(3//)-one analogues. Treatment of 2-aminobenzonitrile with 3-phenyl-acryloyl chloride followed by oxidative ring closure, gave the desired quinazolinone in 29% yield. 6-Chloro derivatives of this class of compounds, independently prepared by Hamel and co-workers (not shown), were shown to have growth inhibitory activity against leukemia cells. 

Documented effects Compounds isolated from the roots exhibited leishmanicidal activity in vitro and inhibited growth of cultured malaria parasites, human lymphocytes, and human carcinoma cell lines (Sairafianpour et al. 2001). Compounds isolated from the aboveground parts exhibited cytotoxic activity against leukemia cells (Aoyagi et al. 2006). 

A solid-phase combinatorial approach was used to synthesize nucleosides containing triazine-and pyrimidine-based exocyclic analogs of clitocine (194, R" = R = H), a fungal metabolite that exhibits potent cytostatic effects against leukemia cell lines through the inhibition of adenosine kinase as well as insecticidal activity (Figme 11.89). The initial library 195 of 1234 compounds was prepared by successive reaction of a 4,6-dichloro-substituted precursor attached to... 

Plant extracts are continuously being tested for bioactivity, and in cancer research, major enterprises for screens of antiproliferative activity are sometimes carried out. In one of these screens, nearly 70,000 species of terrestrial plants were tested against leukemia cell lines [95]. The authors labeled plant genera as hot if they yielded three or more plant species that showed activity in the screens. Six Psychotria species gave active extracts, so Psychotria earned the title of hot genus [95], This type of approach, extensive analysis of plant extracts in the search of bioactive phytochemicals, is very expensive, time-consuming, and labor-intensive, but can unveil precious new drug leads, as was the case with paclitaxel [96]. 

SkE [58]. New assays against leukemia should be conducted with quassinoids as SkE and/or bmceantin are strongly active against leukemia cell lines in which Ras/Raf/MEK/Erk and c-MYC are activated. 

Substituted 1,2,3,4-tetrahydroquinolines are present in several natural products, and the synthesis of some of those have been achieved starting with a Povarov reaction [197], For example, luotonin A 502, with a rather simple structure but promising cytotoxicity against leukemia cells, was the target of a four-step total synthesis, which involves a Povarov reaction combined with an oxidation to build the quinoline intermediate 501 (Scheme 13.106) [197c],... 

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