A novel thiazolidine compound induces caspase-9 dependent apoptosis in cancer cells

The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on l...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2012-09, Vol.20 (17), p.5094-5102
Main Authors: Onen-Bayram, F. Esra, Durmaz, Irem, Scherman, Daniel, Herscovici, Jean, Cetin-Atalay, Rengul
Format: Article
Language:English
Subjects:
anticarcinogenic activity
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Biological and medical sciences
Cancer
Caspase 9 - metabolism
Caspase-9
Cell cycle
Cell Line, Tumor
chemical structure
chemogenomics
Colon
Colon cancer
Cytotoxic
Cytotoxicity
death
death receptors
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Endometrium
Hepatocytes
Humans
inhibitory concentration 50
Liver
Medical sciences
Neoplasms - enzymology
Neoplasms - pathology
Pharmacology. Drug treatments
Structure-Activity Relationship
Terminal alkyne
Thiazolidine
Thiazolidines - chemical synthesis
Thiazolidines - chemistry
Thiazolidines - pharmacology
Tumor cell lines
uterine neoplasms
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The forward chemogenomics strategy allowed us to identify a potent cytotoxic thiazolidine compound as an apoptosis-inducing agent. Chemical structures were designed around a thiazolidine ring, a structure already noted for its anticancer properties. Initially, we evaluated these novel compounds on liver, breast, colon and endometrial cancer cell lines. The compound 3 (ALC67) showed the strongest cytotoxic activity (IC50 ∼5μM). Cell cycle analysis with ALC67 on liver cells revealed SubG1/G1 arrest bearing apoptosis. Furthermore we demonstrated that cytotoxicity of this compound was due to the activation of caspase-9 involved apoptotic pathway, which is death receptor independent.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2012.07.016