Fingerprint-based similarity search identified p-anisidine as an anticancer agent in HeLa and a prospective phytochemical ETV1 transcription factor inhibitor

Abstract

Overexpression of E26 transformation-specific (ETS) PEA3 subfamily transcription factor (TF) ETV1 is reportedly oncogenic and metastatic in several cancers. Albeit, a few synthetic small molecule inhibitors of ETV1 have been identified to date. In this context, we hereby proposed a phytochemical lead development scheme to gather inhibitor scaffolds for ETV1. A fingerprint-based similarity search was conducted to screen plant compounds structurally similar to known ETV1 perturbagens. At default cutoffs, 20 compounds were retrieved whose pharmacokinetic, docking, and scaffold analysis rendered eight compounds for final evaluation in HeLa cells by MTT assay. CID7732 (p-anisidine) belonging to the subclass aminophenyl ethers was emerged as a promising anticancer agent with an IC50 of 27.769 µg/mL. This is the first natural product-based chemical hunt carried out for ETV1 repressors.

Communicated by Ramaswamy H. Sarma

Keywords:

• Similarity search
• p-anisidine
• anticancer
• HeLa

Acknowledgements

We are grateful to DBT-BIF Centre at State Inter-University Centre of Excellence in Bioinformatics (SIUCEB) in Department of Computational Biology and Bioinformatics, University of Kerala for the additional support. Special thanks to Prof P. R. Sudhakaran for his active participation and valuable inputs.

Disclosure statement

No potential conflict of interest was reported by the authors.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work is supported by the Grant received from Kerala State Council for Science, Environment, and Technology (KSCSTE).