Title: Bis[3,5-bis(benzylidene)-4-oxo-1-piperidinyl]amides: A Novel Class of Potent Cytotoxins
Authors: Das, Swagatika ×
Das, Umashankar
Varela-Ramírez, Armando
Lema, Carolina
Aguilera, Renato J
Balzarini, Jan
De Clercq, Erik
Dimmock, Stephen G
Gorecki, Dennis K J
Dimmock, Jonathan R #
Issue Date: Oct-2011
Publisher: Wiley - V C H Verlag GmbH & Co. KGaA
Series Title: ChemMedChem vol:6 issue:10 pages:1892-9
Article number: 10.1002/cmdc.201100199
Abstract: The principal objective of this study was the examination of the theory of cytotoxic synergism. In this exploratory study, we tested the hypothesis that doubling the number of sites available for thiol alkylation in a series of candidate cytotoxins increases potency more than two-fold. This concept was verified in one-third of our comparisons using human Molt 4/C8 and CEM T-lymphocytes and murine L1210 cells. In addition, the significant potencies of various members of our compound series justified further studies. Molecular modeling revealed that relative locations of the amidic groups correlate with cytotoxicity. A potent cytotoxic compound, 1,2-bis(3,5-dibenzylidene-4-oxo-piperidin-1-yl)ethane-1,2-dione (1 a) inhibited the growth of a large number of human tumor cell lines and displayed greater toxicity toward certain non-adherent cells than toward adherent neoplasms or fibroblasts. The mode of action of 1 a includes induction of apoptosis and necrosis.
ISSN: 1860-7179
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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