Cytotoxic 1,3-diarylidene-2-tetralones and related compounds.
A number of 1,3-arylidene-2-tetralones 1, 2 and 4 were synthesised and demonstrated cytotoxic activity towards murine P388 and L1210 cells as well as human Molt 4/C8 and CEM T-lymphocytes. In general, the related 1-arylidene-2-tetralones 3 possessed lower potencies in these screens than the compounds in series 1 and 4. Approximately, half of the compounds were evaluated against a panel of human tumour cell lines. In this screen, most of the enones were more cytotoxic than the established anticancer agent melphalan and some demonstrated selective toxicity towards leukemic and colon cancer cells. The modes of action of representative compounds include interfering with the biosyntheses of nucleic acids and proteins as well as altering redox potentials. The compounds were well tolerated when administered intraperiteonally to mice. Thus these novel enones are promising prototypic molecules due to their potent cytotoxic properties and lack of significant murine toxicity.
Dimmock
Jonathan R
JR
College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan, Canada S7N 5C9. dimmock@skyway.usask.ca
Padmanilyam
Maniyan P
MP
Zello
Gordon A
GA
Quail
J Wilson
JW
Oloo
Eliud O
EO
Prisciak
Jared S
JS
Kraatz
Heinz Bernhard
HB
Cherkasov
Arten
A
Lee
Jeremy S
JS
Allen
Theresa M
TM
Santos
Cheryl L
CL
Manavathu
Elias K
EK
De Clercq
Erik
E
Balzarini
Jan
J
Stables
James P
JP
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry* / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D010084:Oxidation-Reduction; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry* / Q000494:pharmacology*; D013267:Stilbenes / Q000737:chemistry; D013329:Structure-Activity Relationship; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007659:Ketones; D011084:Polycyclic Aromatic Hydrocarbons; D013267:Stilbenes; D013764:Tetrahydronaphthalenes