Please use this identifier to cite or link to this item:
Title: Synthesis and evaluation of functionalized isoindigos as antiproliferative agents
Authors: Wee, X.K.
Yeo, W.K. 
Zhang, B. 
Tan, V.B.C. 
Lim, K.M. 
Tay, T.E. 
Go, M.-L. 
Keywords: Antiproliferative activity
CDK2 inhibition
Molecular modeling
Issue Date: 1-Nov-2009
Citation: Wee, X.K., Yeo, W.K., Zhang, B., Tan, V.B.C., Lim, K.M., Tay, T.E., Go, M.-L. (2009-11-01). Synthesis and evaluation of functionalized isoindigos as antiproliferative agents. Bioorganic and Medicinal Chemistry 17 (21) : 7562-7571. ScholarBank@NUS Repository.
Abstract: A series of functionalized isoindigos structurally related to meisoindigo (1-methylisoindigo), a therapeutic agent used for the treatment of a form of leukemia, were synthesized and evaluated for antiproliferative activities on a panel of human cancer cells. Two promising compounds (1 -phenpropylisoindigo and 1-(p-methoxy-phenethyl)-isoindigo) that were more potent than meisoindigo and comparable to 6bromoindirubin-3'-oxime on leukemic K562 and liver HuH7 cells were identified. Structure-activity relationships showed the importance of keeping one of the lactam NH in an unsubstituted state. Substitution of the other lactam NH with aryl or arylalkyl side chains retained or improved activity in most instances. An intact exocyclic double bond was also essential, possibly to maintain planarity and rigidity of the isoindigo scaffold. None of the compounds were found to inhibit CDK2 in an in vitro assay, in spite of reports linking the antiproliferative activities of meisoindigo and other isoindigos to CDK2 inhibition. Hence, these functionalized isoindigos disrupted cell growth and proliferation by other mechanistic pathways that did not involve CDK2 inhibition. © 2009 Elsevier Ltd. All rights reserved.
Source Title: Bioorganic and Medicinal Chemistry
ISSN: 09680896
DOI: 10.1016/j.bmc.2009.09.008
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Jan 24, 2022


checked on Jan 24, 2022

Page view(s)

checked on Jan 27, 2022

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.