Molecular docking, 3D-QSAR, molecular dynamics, synthesis and anticancer activity of tyrosine kinase 2 (TYK 2) inhibitors

Abstract

A therapeutic rationale is proposed by selectively targeting tyrosine kinase 2 (TYK 2) to obtain potent TYK 2 inhibitors by molecular modeling studies. In the present study, we have taken tyrosine kinase (TYK 2) inhibitors and carried out molecular docking, 3 D quantitative structure–activity relationship (3D-QSAR) analysis and molecular dynamics (MD). Based on the 3D-QSAR results thirteen new compounds (R-1 to R-13) were designed and synthesized in good yields. The synthesized molecules were evaluated for their in vitro anticancer activity against LnCap and A549 cell lines. The molecules R-1, R-3, R-5, R-7, and R-10 exhibited considerable anti cancer activity.

Keywords:

• CoMFA (Comparative molecular field analysis)
• CoMSIA (Comparative molecular similarity indices analysis)
• PLS (partial least square) analysis
• TYK 2(Tyrosine kinase 2)

Acknowledgements

We gratefully acknowledge TriposInc, USA and Schrödinger LLC, New York for providing us the software. We wish to express our gratitude to Department of Chemistry, Osmania University for providing facilities to carry out the research work.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was made possible through grants from DST-SERB (SB/EMEQ-004/2013), CSIR (01/(2436)/10/EMR-II), DST-PURSE-II/2017 and UGC/UPE/FAR/OU/2017 New Delhi, India. Dr.Venugopal Akula IICT Hyderabad for mass spectral studies and author’s RI and SB would like to acknowledge financial support from UGC for research fellowships.