NDLI: A novel 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivative inhibits tumor cell invasion and potentiates the apoptotic effect of TNFα by abrogating NF-κB activation cascade

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A novel 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivative inhibits tumor cell invasion and potentiates the apoptotic effect of TNFα by abrogating NF-κB activation cascade

Content Provider	Springer Nature Link
Author	Ningegowda, Raghu Shivananju, Nanjunda Swamy Rajendran, Peramiyan Rangappa, Kanchugarakoppal S. Chinnathambi, Arunachalam Li, Feng Achar, Raghu Ram Shanmugam, Muthu K. Bist, Pradeep Alharbi, Sulaiman Ali Lim, Lina Hsiu Kim Sethi, Gautam Priya, Babu Shubha
Copyright Year	2016
Abstract	Condensed-bicyclic 4,6-substituted1,2,4-triazolo-1,3,4-thiadiazole derivatives (CBTT) have been shown to possess a wide spectrum of pharmacological activities. In this study, several novel CBTT derivatives were synthesized and investigated for their possible role as anti-neoplastic agents. The anti-proliferative effect of various CBTT derivatives was analyzed against tumor cell lines by (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. One of the potential CBTT derivative, 5-(3-(2,3-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-6-yl)flurobenzonitrile (DTTF) was found to be the most potent against cervical cancer SiHa cells and exhibited minimal effect against normal cells. Molecular docking analysis indicated that transcription factor NF-κB was one of the potential molecular targets modulated by DTTF. Specifically, the drug blocked the TNFα-induced phosphorylation of upstream IκBα kinase in a time-dependent manner leading to the suppression of NF-κB activation and nuclear translocation. DTTF also potentiated the apoptotic effect of TNFα, as well as significantly inhibited migration and invasion of tumor cells. Overall, these findings indicate a potential novel role and mechanism(s) of action of DTTF as an anticancer agent against diverse malignancies.
Starting Page	145
Ending Page	157
Page Count	13
File Format	PDF
ISSN	13608185
Journal	Apoptosis
Volume Number	22
Issue Number	1
e-ISSN	1573675X
Language	English
Publisher	Springer US
Publisher Date	2016-11-24
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Apoptosis TNFa NF-kB Invasion Thiadiazole Cancer Research Cell Biology Oncology Biochemistry Virology
Content Type	Text
Resource Type	Article
Subject	Pharmaceutical Science Biochemistry (medical) Cell Biology Clinical Biochemistry Cancer Research Pharmacology

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