Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro cytotoxicity of etoposide against mouse P388 leukemia cells was kinetically studied and compared with those of podophyllotoxin, the parent compound, and other antitumor agents. When P388 cells were exposed to etoposide, surviving-cell fraction decreased with etoposide concentration and exposure time. Similar results were obtained with doxorubicin, peplomycin and cisplatin. The cytotoxicity of melphalan was dependent on concentration but scarcely on exposure time. From these data, n in Cn X T = K where T, C and K are exposure time, concentration required for killing 90% of P388 cells and a constant, respectively, was calculated. Etoposide gave an n value of 1.16. n values for doxorubicin, peplomycin and cisplatin, all belonging to the Shimoyama type Ib group where the cytotoxicity of the agent depends on both concentration and exposure time, were 1.29, 1.28 and 3.03, respectively. The n value for melphalan, belonging to the type Ia group where cytotoxicity depends only on concentration, was 54.0. From these results, it was concluded that etoposide is of type Ib. The cytotoxicities of podophyllotoxin, 5-fluorouracil, cytarabine and vinblastine were greatly dependent on exposure time. Podophyllotoxin may be an agent of type II whose cytotoxicity depends only on exposure time.
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PMID:[Kinetics of etoposide cytotoxicity against mouse P388 leukemia]. 241 68

Podophyllotoxin is a well-known natural antitumor agent with severe side effects, which led us to synthesize its numerous analogs in search of product(s) of improved therapeutic potential. Here, we report an efficient method for the synthesis of a series of 4-O-podophyllotoxin estolides with spectral characteristics and their biological studies. The OH of a known molecule, 4-O-podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate 2, was coupled with the carboxylic groups of different FA with the help of dicyclohexylcarbodiimide and dimethyl aminopyridine (catalyst) to produce high yields of their respective C(4)alpha-estolides 3-11. Spectroscopic techniques, particularly 1H and 13CNMR, proved to be suitable tools to characterize the new compounds. These molecules of greater lipophilic character were tested for their in vitro cytotoxicity against four human solid tumors, one human leukemia cell, and one noncancerobu cell. Compounds 4-6 and 11 showed moderate antileukemic activity; unexpectedly, none were found to be active against solid tumors. Estolides were also investigated for their in vitro activity against tubulin and topoisomerase II proteins. All the compounds showed inhibition of the catalytic activity of topoisomerase II, whereas 6-8 also inhibited tubulin polymerization. These results suggest the need for further screening of these molecules against a larger panel of cancerous cells.
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PMID:Synthesis, spectroscopic, and biological studies of novel estolides derived from anticancer active 4-O-podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate. 1558 23