Cytotoxic 1,3-diarylidene-2-tetralones and related compounds
Dimmock, Jonathan R × Padmanilyam, Maniyan P Zello, Gordon A Quail, J Wilson Oloo, Eliud O Prisciak, Jared S Kraatz, Heinz Bernhard Cherkasov, Arten Lee, Jeremy S Allen, Theresa M Santos, Cheryl L Manavathu, Elias K De Clercq, Erik Balzarini, Jan Stables, James P #
European journal of medicinal chemistry vol:37 issue:10 pages:813-24
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.