Antitumor agents XLII: Comparison of antileukemic activity of helenalin, brusatol, and bruceantin and their esters on different strains of P-388 lymphocytic leukemic cells.
Based on the fact that some known antineoplastic agents possess an ester moiety within their structure, the esters of helenalin, a sesquiterpene lactone, and of brusatol and bruceantin, quassinoids, were synthesized and tested for antileukemic activity in the P-388 screen. These agents gave different T/C% values dependent on the P-388 lymphocytic leukemia strain and the host strain of mice used. Later studies demonstrated that the agents caused different degrees of inhibition of nucleic acid and protein synthesis in the various P-388 strains. The higher the degree of inhibition of precursor incorporation into the nucleic acid or protein, the higher was the T/C% value obtained in a given P-388 strain. The study demonstrates the lack of consistency of P-388 lymphocytic leukemia cell lines used in various laboratories and indicates that the inbred strain of mice is a critical factor in the tolerance of drug toxicity and, thus, T/C% obtained.
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005900:Glaucarubin / Q000031:analogs & derivatives / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy* / Q000378:metabolism; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010616:Phenanthrenes / Q000494:pharmacology*; D036702:Quassins; D012717:Sesquiterpenes / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane; D013936:Thymidine / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010616:Phenanthrenes; D036702:Quassins; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C020237:brusatol; C001329:helenalin; D005900:Glaucarubin; C002550:bruceantin; D013936:Thymidine