Anticancer Potential of Hydroxychavicol Derived from Piper betle L: An in Silico and Cytotoxicity Study

Abstract

Piper betle L. is a popular medicinal plant in Asia, and extracts of the plant leaf are used for several therapeutics. It is known for its rich source of phenolic compounds, including hydroxychavicol. Hydroxychavicol is an allylbenzene that has gained much attention due to its anticancer properties. The current study quantified and purified hydroxychavicol from P. betle L. and predicted its anticancer competence through in silico and cytotoxicity studies. Leaf samples of 22 P. betle L. accessions from different locations of Tamil Nadu, India, were analyzed using reverse phase-high performance liquid chromatography for quantification of hydroxychavicol. The highest quantity of hydroxychavicol was obtained from the accession BV22 (89.2%). Chemical absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of hydroxychavicol using SwissADME satisfied the physicochemical property guidelines of Lipinski’s Rule of Five, ensuring its drug-likeness behavior. Molecular docking studies confirmed the interaction of hydroxychavicol with all 16 tested cancer targets. In Vitro MTT assay of hydroxychavicol in bone cancer cell lines (MG63) also demonstrated the anticancer competency, indicating the requirement to formulate the molecule as a drug in treating various types of cancers.

Acknowledgments

Throughout the research, financial assistance was provided by the Indian Council of Medical Research (ICMR), New Delhi, through the ICMR-JRF fellowship. The infrastructure facility available at the Bioinformatics Laboratory, Centre for Plant Molecular Biology and Biotechnology, Tamil Nadu Agricultural University, Coimbatore supported by the Biotechnology Information System (BTIS) Program of the Department of Biotechnology (DBT), Government of India, New Delhi is gratefully acknowledged.

Disclosure Statement

The authors declare that there is no conflict of interest.

Authors Contribution

Vinusri S, Gnanam R, Santhanakrishnan V P, Caroline R, and Kandavelmani A conceived the ideas and planned the experiments. Vinusri S performed the extraction and purification of hydroxychavicol, HPLC experiments, ADMET and molecular docking studies, In Vitro cytotoxic studies, and manuscript preparation. Gnanam R was in charge of the overall workframe, facilitated the initial sample collection, verified the methods, analyzed the results, supervised the findings, and structured the entire manuscript. Santhanakrishnan V P provided academic support for sample preparation and analysis of HPLC results. Caroline R supervised ADMET analysis and docking experiments, supported the interpretation of results, and shaped its corresponding writing part in the manuscript. Kandavelmani A contributed ideas for initial studies on docking tabulations. All authors provided substantial feedback, discussed the results, and contributed to the final manuscript.

Additional information

Funding

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