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

Raghu, N. and Nanjunda Swamy, S. and Rajendran, P. and Basappa and Rangappa, K. S. and Chinnathambi, Arunachalam and Li, Feng and Achar, Raghu Ram and Shanmugam, Muthu K. and Bist, Pradeep and Alharbi, Sulaiman Ali and Lim, Lina Hsiu Kim and Sethi, Gautam and Priya, B. S. (2017) 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. Apoptosis, 22 (1). pp. 145-157. ISSN 1573-675X

Text 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.pdf - Published Version Restricted to Registered users only Download (1MB) | Request a copy

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)-1,2,4triazolo3,4-b1,3,4thiadiazol-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-$\kappa$B was one of the potential molecular targets modulated by DTTF. Specifically, the drug blocked the TNF$\alpha$-induced phosphorylation of upstream I$\kappa$B$\alpha$ kinase in a time-dependent manner leading to the suppression of NF-$\kappa$B activation and nuclear translocation. DTTF also potentiated the apoptotic effect of TNF$\alpha$, 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.

Item Type:	Article
Uncontrolled Keywords:	Apoptosis, TNFa, NF-kB, Invasion, Thiadiazole
Subjects:	C Chemical Science > Chemistry
Divisions:	Department of > Chemistry
Depositing User:	C Swapna Library Assistant
Date Deposited:	17 Jun 2019 05:13
Last Modified:	11 Jul 2022 10:08
URI:	http://eprints.uni-mysore.ac.in/id/eprint/3212

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