Researchers from Acadia University report on findings in leukemia
2007 NOV 19 -- According to recent research from Wolfville, Canada, "A series of E,E,E-3,5-bis(arylidene)-1-(4-arylamino-4-oxo-2-butenoyl)-4-piperidones 4 (phenylidene) and 5 (4-nitrophenylidene) were prepared in order to explore the structural features of the N-acyl group which affects the cytotoxic potency. Evaluation toward human Molt 4/C8 and CEM T-lymphocytes revealed that many of the IC50 figures were submicromolar and lower than melphalan." "Marked inhibitory potencies toward murine leukemia L1210 cells were also noted. When evaluated against a panel of human tumor cell lines, three representative compounds in series 4 displayed selective toxicity to leukemia and colon cancer cell lines and were significantly more potent than the reference drug melphalan," wrote A. Jha and colleagues, Acadia University. The researchers concluded: "Molecular modeling of representative compounds in both series 4 and the analogs, in which the configuration of the olefinic double bond was changed from E to Z (series 3), revealed that the torsion angles of the arylidene aryl rings and locations of the terminal arylaminocarbonyl groups may have contributed to the greater cytotoxic properties displayed in 3. Compounds 4c (3,4-dichlorophenylamino), d (4-methylphenylamino) and 5c (3,4-dichlorophenylamino), d (4-methylphenylamino) inhibited the activity of human N-myristoyltransferase by approximately 50% at concentrations of 50-100 mc M. The compounds in series 4 and 5 were well tolerated in a short-term toxicity study in mice." Jha and colleagues published their study in Bioorganic & Medicinal Chemistry (E,E,E-1-(4-Arylamino-4-oxo-2-btitenoyl)-3,5-bis(Arylidene)-4piperidones: A topographical study of some novel potent cytotoxins. Bioorganic & Medicinal Chemistry, 2007;15(17):5854-5865). For additional information, contact A. Jha, Acadia University, Dept. of Chemical, Wolfville, NS B4P 2R6, Canada. Publisher contact information for the journal Bioorganic & Medicinal Chemistry is: Pergamon-Elsevier Science Ltd., the Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, England. Keywords: Canada, Wolfville, Hematology, Leukemia, Oncology, Acadia University. This article was prepared by Hematology Week editors from staff and other reports. Copyright 2007, Hematology Week via NewsRx.com.
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