title: In vitro cytotoxicity evaluation of some substituted isatin derivatives.
abstract: A range of substituted 1H-indole-2,3-diones (isatins) were synthesized using standard procedures and their cytotoxicity evaluated against the human monocyte-like histiocytic lymphoma (U937) cell line in vitro. SAR studies identified C(5), C(6), and C(7) substitution greatly enhanced activity with some di- and tri-halogenated isatins giving IC(50) values <10 microM. Of the 23 compounds tested, four were selected for further screening against a panel of five human cancer cell lines. These compounds, in general, showed greater selectivity toward leukemia and lymphoma cells over breast, prostate, and colorectal carcinoma cell lines. The most active compound, 5,6,7-tribromoisatin (2p), was found to be antiproliferative at low micromolar concentrations and also activated the effector caspases 3 and 7 in a dose-dependent manner. These results indicate that di- and tri-substituted isatins may be useful leads for anticancer drug development in the future.
authors.affiliation: School of Biological Sciences, University of Wollongong, NSW 2522, Australia. klv04@uow.edu.au
authors.forename: Kara L
authors.initials: KL
authors.lastname: Vine
authors.forename: Julie M
authors.initials: JM
authors.lastname: Locke
authors.forename: Marie
authors.initials: M
authors.lastname: Ranson
authors.forename: Kirsten
authors.initials: K
authors.lastname: Benkendorff
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Pyne
authors.forename: John B
authors.initials: JB
authors.lastname: Bremner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors; D020536:Enzyme Activators / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007510:Isatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007510:Isatin; D051357:Cyclin-Dependent Kinase 2; D053148:Caspase 3; D053179:Caspase 7