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Synthesis and Characterization of Plumbagin S-Allyl Cysteine Ester: Determination of Anticancer Activity In Silico and In Vitro

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Abstract

In recent years, derivatives of natural compounds are synthesized to increase the bioavailability, pharmacology, and pharmacokinetics properties. The naphthoquinone, plumbagin (PLU), is well known for its anticancer activity. However, the clinical use of PLU is hindered due to its toxicity. Previous reports have shown that modification of PLU at 5ʹ-hydroxyl group has reduced its toxicity towards normal cell line. In accordance, in the present study, 5ʹ-hydroxyl group of PLU was esterified with S-allyl cysteine (SAC) to obtain PLU-SAC ester. The drug-likeness of PLU-SAC was understood by in silico ADME analysis. PLU-SAC was characterized by UV–visible spectroscopy, mass spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. Molecular docking and dynamics simulation analysis revealed the interaction of PLU-SAC with proteins of interest in cancer therapy such as human estrogen receptor α, tumor protein p53 negative regulator mouse double minute 2, and cyclin-dependent kinase 2. MMGBSA calculation showed the favorable binding energy which in turn demonstrated the stable binding of PLU-SAC with these proteins. PLU-SAC showed apoptosis in breast cancer cell line (MCF-7) by inducing oxidative stress, disturbing mitochondrial function, arresting cells at G1 phase of cell cycle, and initiating DNA fragmentation. However, PLU-SAC did not show toxicity towards normal Vero cell line. PLU-SAC was synthesized and structurally characterized, and its anticancer activity was determined by in silico and in vitro analysis.

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Acknowledgements

Mrs. V. Sudha acknowledges Periyar University for the award of University Research Fellowship. Dr. S. Penislusshiyan acknowledges Human Resource Development, Department of Health Research, Ministry of Health and Family Welfare, India, for the award of young scientist fellowship (Ref. No. R.12014/51/2020-HR). The authors thank the Department of Computer Science, Periyar University, for providing the high-performance computer facility.

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Authors and Affiliations

  1. Department of Biochemistry, Periyar University, Salem, Tamil Nadu, 636011, India

    Sudha Vijayan, Chitra Loganathan, Penislusshiyan Sakayanathan & Palvannan Thayumanavan

  2. Research and Development Center, Bioinnov Solutions LLP, Salem, Tamil Nadu, 636002, India

    Chitra Loganathan

Authors
  1. Sudha Vijayan
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  2. Chitra Loganathan
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  3. Penislusshiyan Sakayanathan
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  4. Palvannan Thayumanavan
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by SV. Analysis, supervision of the work, and manuscript preparation were done by CL. In silico analysis was carried out by PS. Supervision of the work, correction, review and editing of the manuscript was done by PT. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Palvannan Thayumanavan.

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Vijayan, S., Loganathan, C., Sakayanathan, P. et al. Synthesis and Characterization of Plumbagin S-Allyl Cysteine Ester: Determination of Anticancer Activity In Silico and In Vitro. Appl Biochem Biotechnol 194, 5827–5847 (2022). https://doi.org/10.1007/s12010-022-04079-0

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  • DOI: https://doi.org/10.1007/s12010-022-04079-0

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