A profile of the in vitro anti-tumor activity of imidazolium-based ionic liquids.
The anti-cancer activity and cytotoxicity of imidazolium-based ionic liquids has been determined for the first time via NCI's in vitro 60 human tumor cell lines. The preliminary SAR showed that the chain length of alkyl substitution at N-3 position of imidazole ring plays crucial role towards anti-tumor activity and cytotoxicity of these ionic liquids. The ionic liquids with alkyl substitution of C-12 chain length were found to be effective against all 60 tumor cell lines and show very low cytotoxicity in most of the cases. Further increase in chain length resulted in enhanced growth inhibition of tumor cell lines as well as high cytotoxicity. Interestingly, active compounds 1-dodecyl-3-methylimidazolium chloride (8), 1-dodecyl-3-methylimidazolium tetrafluoroborate (9), 1-hexadecyl-3-methylimidazoium chloride (10), 1-octadecyl-3-methylimidazolium chloride (11), 1-octadecyl-3-methylimidazolium hexafluorophosphate (12), 1-octadecyl-3-methylimidazolium bis(triflic)imide (13) and 1-octadecyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate (14) were highly active against leukemia cell lines, especially compounds 13 and 14 where the cytotoxicity was also very low as given by LC(50) >100microM in all six leukemia cell lines.
Malhotra
Sanjay V
SV
Laboratory of Synthetic Chemistry, SAIC-Frederick Inc., National Cancer Institute at Frederick, 1050 Boyles Street, Frederick, MD 21702, USA. malhotrasa@mail.nih.gov
Kumar
Vineet
V
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D052578:Ionic Liquids / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship; D005466:Fluorocarbons
D000970:Antineoplastic Agents; D007093:Imidazoles; D052578:Ionic Liquids; C548715:1-octadecyl-3-methylimidazolium; D005466:Fluorocarbons