Targeting bone cancer with 4-Allylbenzene-1,2-diol purified from Piper betle L.: an in silico and cytotoxicity scrutiny

Abstract

Piper betle L., a well-known medicinal plant with rich source of bioactive compounds, is widely used in several therapeutics. The present study was performed to scrutinize the anti-cancer potential of compounds P. betle petiole by means of in silico studies, purification of 4-Allylbenzene-1,2-diol from petioles and assessing its cytotoxicity on bone cancer metastasis. Subsequent to SwissADME screening, 4-Allylbenzene-1,2-diol and Alpha terpineol were chosen for molecular docking together with eighteen approved drugs against fifteen important bone cancer targets accompanied with molecular dynamics simulation studies. 4-Allylbenzene-1,2-diol was found to be multi-targeting, interacted effectively with all targets, particularly exhibited good stability with MMP9 and MMP2 during molecular dynamics simulations and Molecular Mechanics- Generalized Born and Surface Area (MM-GBSA) analysis using Schrodinger. Later, the compound was isolated, purified and the cytotoxicity studies on MG63 bone cancer cell lines confirmed the cytotoxicity nature (75.98% at 100 µg/ml concentration). The results demonstrated the compound as a matrix metalloproteinase inhibitor, and therefore 4-Allylbenzene-1,2-diol may possibly be prescribed in targeted therapy for alleviating the bone cancer metastasis upon further wet lab experimental validations.

Communicated by Ramaswamy H. Sarma

Keywords:

• Betelvine
• petioles
• 4-Allylbenzene-1,2-diol
• multi-targeting therapy
• bone cancer

Acknowledgements

Throughout the study, the financial assistance from Indian Council of Medical Research, New Delhi through ICMR-JRF fellowship, the academic support and lab facilities from Bioinformatics Laboratory, Centre for Plant Molecular Biology and Biotechnology, Tamil Nadu Agricultural University, Coimbatore supported by Biotechnology Information System (BTIS) Program of Department of Biotechnology (DBT), Government of India, New Delhi and Prof. R. Sowdhamini‘s lab, National Centre for Biological Sciences (NCBS-TIFR), Bengaluru are gratefully acknowledged.

Compliance with ethical standards

Disclosure statement

The authors declared that there is no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Funding

This work was supported by Indian Council of Medical Research, New Delhi through ICMR JRF fellowship (No.3/1/3/JRF-2018/HRD-4 (62009) dt 16.11.2018).