Title: Cytotoxic 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienes mounted on alicyclic scaffolds
Authors: Das, Umashankar ×
Gul, H Inci
Alcorn, Jane
Shrivastav, Anuraag
George, Theresa
Sharma, Rajendra K
Nienaber, Kurt H
De Clercq, Erik
Balzarini, Jan
Kawase, Masami
Kan, Noriyuki
Tanaka, Toru
Tani, Satoru
Werbovetz, Karl A
Yakovich, Adam J
Manavathu, Elias K
Stables, James P
Dimmock, Jonathan R #
Issue Date: May-2006
Series Title: European Journal of Medicinal Chemistry vol:41 issue:5 pages:577-585
Abstract: The 5-aryl-1-(4-nitrophenyl)-3-oxo-1,4-pentadienyl pharmacophore was incorporated into four series of compounds 1-4. Compounds 1a-g comprised a cluster of 3-arylidene-1-(4-nitrophenylmethylene)-2-oxo-3,4-dihydro-1H-naphthalenes while the analogues 2a-g consisted of a group of 6-arylidene-2-(4-nitrophenylmethylene)cyclohexanones. Three other compounds prepared in this study were 1-(4-nitrophenylmethylene)-3-(3,4,5-trimethoxyphenylmethylene)-2-oxo-2,3-dihydro-1H-indene 3a as well as two 5-arylidene-2-(4-nitrophenylmethylene)cyclopentanones 4a,b. The compounds were evaluated against human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 cells. In general, the compounds in series 1 displayed marked cytotoxicity having IC50 values in the 1-5 microM range while the related cyclohexyl analogues in series 2 were slightly less potent (IC50 figures were mainly 5-10 microM). The relative locations of two aryl rings present in all four series were considered to contribute significantly to bioactivity and may have accounted for the virtual absence of cytotoxic properties in series 3 and 4. Most of the compounds were administered intraperitoneally to mice using doses up to and including 300 mg/kg. No mortalities were noted. The inhibiting effect of most of the compounds towards Helicobacter pylori is noteworthy. The modes of action of representative compounds include the induction of apoptosis while some compounds weakly inhibited tubulin polymerisation and human N-myristoyltransferase.
ISSN: 0223-5234
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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