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 compound...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2002-10, Vol.37 (10), p.813-824
Main Authors: Dimmock, Jonathan R, Padmanilyam, Maniyan P, Zello, Gordon A, Wilson Quail, J, 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
Format: Article
Language:English
Subjects:
2-Tetralones
Animals
Antineoplastic agents
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Crystallography, X-Ray
Cytotoxicity
Drug Screening Assays, Antitumor
General aspects
Humans
Inhibitory Concentration 50
Ketones - chemistry
Ketones - pharmacology
Leukemia L1210 - drug therapy
Leukemia P388 - drug therapy
Medical sciences
Mice
Murine toxicity
Oxidation-Reduction
Pharmacology. Drug treatments
Polycyclic Aromatic Hydrocarbons - chemistry
Polycyclic Aromatic Hydrocarbons - pharmacology
Redox potentials
Stilbenes - chemistry
Structure-Activity Relationship
T-Lymphocyte Subsets - drug effects
Tetrahydronaphthalenes - chemistry
Tetrahydronaphthalenes - pharmacology
Tumor Cells, Cultured
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Summary: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.
ISSN:0223-5234
1768-3254
DOI:10.1016/S0223-5234(02)01402-2