Computational Insights into Pharmacokinetic Profiling of Amygdalin: An In-Silico Study

Authors

  • Himanshu Sachdeva
  • Sunishtha Kalra Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.
  • Kaushal Arora Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.
  • Praveen Kumar Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India
  • Yogesh Verma Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.
  • Aditya Bhushan Pant Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.
  • Govind Singh Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.

DOI:

https://doi.org/10.53555/jaz.v43i1.935

Keywords:

Amygdalin, ADME Prediction, Cyanogenic Glycosides, Pharmacokinetics, In-Silico Modeling

Abstract

Amygdalin is a naturally occurring cyanogenic glycoside which has been used as an alternative anti-cancer agent despite controversies surrounding its efficacy and safety. This study utilized computational approaches to investigate the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of amygdalin based on its molecular structure. Amygdalin was modeled in ChemBio3D and submitted to SwissADME and admetSAR servers for ADMET parameter prediction. The in-silico simulations indicated suboptimal pharmacological properties for amygdalin, including low lipophilicity, poor bioavailability, minimal blood-brain barrier permeability and non-compliance with drug-likeness criteria. Additional pharmacokinetic modeling through Simcyp suggested rapid clearance and short half-life after intravenous administration.While toxicity was predicted to be low at regular dosages, the overall pharmacological limitations may pose challenges for amygdalin’s efficacy as an anti-cancer therapy. The computational findings provide comprehensive insights into amygdalin’s drug-like behavior and can inform future in vitro/in vivo investigations on this naturally derived compound.

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References

Newman DJ, Cragg GM. (2016). Natural Products as Sources of New Drugs from 1981 to 2014. Journal of

Natural Products, 79(3), 629-61.

Musilova, J., Lidikova, J., Vollmannova, A., Frankova, H., Urminska, D., Bojnanska, T., & Toth, T. (2020).

Influence of heat treatments on the content of bioactive substances and antioxidant properties of

sweet potato (Ipomoea batatas L.) tubers. Journal of Food Quality, 2020.

Zhou C, Qian L, Ma H, Yu X, Zhang Y, Qu W, et al. (2012). Enhancement of amygdalin activated with β-Dglucosidase on HepG2 cells proliferation and apoptosis. Carbohydrate Polymers, 90(1), 516-23.

Chang HK, Shin MS, Yang HY, Lee JW, Kim YS, Lee MH, et al. (2006). Amygdalin induces apoptosis through

regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells.

Biological and Pharmaceutical Bulletin, 29(8), 1597-602.

Guć, M., Rutecka, S., & Schroeder, G. (2020). Analysis of Amygdalin in Various Matrices Using Electrospray

Ionization and Flowing Atmospheric-Pressure Afterglow Mass Spectrometry. Biomolecules, 10(10),

1459.

Favero, G., Bonomini, F., & Rezzani, R. (2021). Pineal gland tumors: a review. Cancers, 13(7), 1547.

Milazzo, S., Ernst, E., Lejeune, S., & Boehm, K. (2006). Laetrile treatment for cancer. Cochrane Database of

Systematic Reviews, (2).

Moertel CG, Fleming TR, Rubin J, Kvols LK, Sarna G, Koch R, et al. (1982). A clinical trial of amygdalin

(Laetrile) in the treatment of human cancer. The New England Journal of Medicine, 306(4), 201-6.Shen, H., Wang, H., Wang, L., Wang, L., Zhu, M., Ming, Y., ... & Lai, E. Y. (2017). Ethanol extract of the root

of Prunus persica inhibited the growth of liver cancer cell HepG2 by inducing cell cycle arrest and

migration suppression. Evidence-Based Complementary and Alternative Medicine, 2017.

Greenberg, D. M. (1980). The case against laetrile. The fraudulent cancer remedy. Cancer, 45(4), 799-807.

Halstead BW, O'Rourke TF, Hood WF, Goldman P. (1988). Amygdalin toxicity studies in rats predict chronic

cyanide poisoning in humans. The Western Journal of Medicine, 149(2), 174-9.

Luang-In, V., Albaser, A. A., Nueno-Palop, C., Bennett, M. H., Narbad, A., & Rossiter, J. T. (2016).

Glucosinolate and desulfo-glucosinolate metabolism by a selection of human gut bacteria. Current

Microbiology, 73, 442-451.

Chen, Y. U., Ma, J., Wang, F., Hu, J., Cui, A., Wei, C., ... & Li, F. (2013). Amygdalin induces apoptosis in

human cervical cancer cell line HeLa cells. Immunopharmacology and Immunotoxicology, 35(1), 43-

51.

Smith DA, Di L, Kerns EH. (2010). The effect of plasma protein binding on in vivo efficacy: misconceptions in

drug discovery. Nature Reviews Drug Discovery, 9(12), 929-39*.

Kharkar, P. S. (2010). Two-dimensional (2D) in silico models for absorption, distribution, metabolism,

excretion and toxicity (ADME/T) in drug discovery. Current Topics in Medicinal Chemistry, 10(1),

116-126*.

Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7(1), 42717*.

Yang, H., Lou, C., Sun, L., Li, J., Cai, Y., Wang, Z., ... & Tang, Y. (2019). admetSAR 2.0: web-service for

prediction and optimization of chemical ADMET properties. Bioinformatics, 35(6), 1067-1069*.

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Published

2022-12-09

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