Anticancer activities of 2,5,8,9-substituted 6-oxo-1,2,3,4,5,6-hexahydrophenanthridines on multi-drug-resistant phenotype cells.
Lycorine is a member of the alkaloid group from the bulb of the amaryllidaceae. This drug has been reported to have anticancer activity. Several synthetic intermediates obtained during the synthetic study of anticancer drugs based on the lycorine structure, were tested for anticancer activity using three cell lines: L1210 and HL60 cell lines which were resistant (R) or sensitive (S) to adriamycin. The two synthetic intermediates, 2-acetoxy- and 2-hydroxy-5-allyl-8,9-methylenedioxy-6-oxo-1,2,3,4,5,6-hexahydr ophenanthridine (1 and 2), both had anticancer activity in all three cell lines. However, the LD50 for the precursors was about 20 fold greater than for the native lycorine. Both 1 and 2 were cytotoxic to the adriamycin-resistant cell line, indicating that these drugs are not affected by the multidrug resistance factors. When low doses of the compounds were used, the HL60R cell line could be induced to differentiate to a cell which expressed a macrophage specific protein. These results suggest that phenanthridines 1 and 2 can be used on cells which are resistant to adriamycin, and that one mechanism of action is the induction of differentiation.
Hua
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DH
Department of Chemistry, Kansas State University, Manhattan 66506, USA. duy@ksu.edu
Saha
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S
Takemoto
D J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D018922:HL-60 Cells; D006801:Humans; D007939:Leukemia L1210; D051379:Mice; D010617:Phenanthridines / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D010617:Phenanthridines