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1,3‐Diaryl‐2‐propenones and 2‐Benzylidene‐1,3‐indandiones: A Quest for Compounds Displaying Greater Toxicity to Neoplasms than Normal Cells
Author(s) -
Pati Hari N.,
Das Umashankar,
Sakagami Hiroshi,
Kawase Masame,
Chu Qing,
Wang Qintao,
Stables James P.,
Dimmock Jonathan R.
Publication year - 2010
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900308
Subject(s) - cytotoxicity , cytotoxic t cell , chemistry , dna fragmentation , apoptosis , toxicity , stereochemistry , cell culture , fragmentation (computing) , biochemistry , programmed cell death , in vitro , biology , genetics , organic chemistry , ecology
A series of 1,3‐diaryl‐2‐propenones 2a–j and analogous 2‐benzylidene‐1,3‐indandiones 3a–j were evaluated against various neoplasms and normal cells. In general, greater cytotoxic potencies and selective toxicity to human malignant cells were observed by the compounds in series 2 rather than 3 . In particular, 2i emerged as a lead molecule having an average CC 50 figure of 8.6 µM and a selective index value of 18. Various physicochemical features of 2a–j were correlated with the cytotoxic potencies to neoplastic cell lines which provide guidelines for expansion of this series of compounds. The enone 2i induced internucleosomal DNA fragmentation and activated caspase‐3 in HL‐60 cells suggesting that one of the ways in which the cytotoxicity of the compounds in series 2 is mediated towards some of the cell lines used in this study is by apoptosis. Neurotoxicity in mice was generally lower in series 2 than 3a–j .