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CC BY 4.0 · Journal of Health and Allied Sciences NU
DOI: 10.1055/s-0044-1792146
Original Article

In Silico Techniques Unveil the Anticancer Potential of Himalayan Pteridophytic Compounds via PI3K Inhibition

Mansi Singh
1   KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh, India
1   KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh, India
,
Priya Bansal   #
1   KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh, India
,
Siddhi Gupta
1   KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh, India
,
Shivani Sharma
1   KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh, India
,
Surya Prakash
1   KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh, India
,
Deepti Katiyar
1   KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh, India
,
Abhishek Kumar   #
1   KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh, India
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Abstract

Introduction Inhibiting the signaling protein/gene involved in cancer progression may affect the signaling cascade and could be a possible targeted approach against progressive cancer. The present study aims to evaluate the anticancer potential of bioactive compounds from selected Himalayan pteridophytes by targeting the phosphoinositide 3 kinase (PI3K) pathway using in silico techniques.

Materials and Methods In the present study, we identified various Himalayan pteridophytes via literature search from different search engines like Google Scholar, Science Direct, PubMed, etc. Among all, four Himalayan pteridophytes were chosen whose bioactive constituents were already identified by gas chromatography–mass spectrometry (GC-MS) analysis. Molecular docking via PyRx software was performed against two PI3K target proteins (PDB ID: 5OQ4 and PDB ID: 3OAW) for determining the binding affinity of selected bioactive constituents against cancer. Drug likeliness and toxicity assessment were also carried out by using Swiss ADME and ProTox-II.

Results and Discussion Molecular docking study identified 12 bioactive molecules with favorable binding affinities (ranging from –7.3 to –10.00 kcal/mol) against PI3K pathway. Among 12 constituents, 3 molecules named as PC-2 (Matteucinol), PC-4 (Matteuorienate-A), and PC-9 (flavan-4-ol) have binding affinity more than the reference compounds. These results suggest that these constituents may serve as a promising candidate for further in vitro and in vivo studies in cancer therapeutics. The selected bioactive compounds demonstrate promising anticancer activity via PI3K inhibition, warranting further experimental validation and development as potential cancer therapeutics.

Keywords

phosphoinositide 3-kinase - anticancer activity - molecular docking - pteridophytes

Authors' Contributions

A.K. contributed to planning, structure, compilation, and finalization of the manuscript. M.S. and P.B. contributed equally and were involved in writing, data generation, and completion of the manuscript. S.S. and S.G. were involved in writing, data generation, and completion of the manuscript. S.P. and D.K. were involved in rechecking of data and completion of the manuscript.


# This paper has equal contribution of both the authors.




Publication History

Article published online:
07 November 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Grover P, Thakur K, Bhardwaj M, Mehta L, Raina SN, Rajpal VR. Phytotherapeutics in cancer: from potential drug candidates to clinical translation. Curr Top Med Chem 2024; 24 (12) 1050-1074
    CrossrefPubMedSearch in Google Scholar
  • 2 Ma X, Yu H. Global burden of cancer. Yale J Biol Med 2006; 79 (3-4): 85-94
    PubMedSearch in Google Scholar
  • 3 Barzegar Behrooz A, Talaie Z, Jusheghani F, Łos MJ, Klonisch T, Ghavami S. Wnt and PI3K/Akt/mTOR survival pathways as therapeutic targets in glioblastoma. Int J Mol Sci 2022; 23 (03) 1353
    CrossrefPubMedSearch in Google Scholar
  • 4 Ortiz-González A, González-Pérez PP, Cárdenas-García M, Hernández-Linares MG. In silico prediction on the PI3K/AKT/mTOR pathway of the antiproliferative effect of O. joconostle in breast cancer models. Cancer Inform 2022; 21: 11 769351221087028
    CrossrefPubMedSearch in Google Scholar
  • 5 Singhal S, Maheshwari P, Krishnamurthy PT, Patil VM. Drug repurposing strategies for non-cancer to cancer therapeutics. Anticancer Agents Med Chem 2022; 22 (15) 2726-2756
    CrossrefPubMedSearch in Google Scholar
  • 6 Baskaran XR, Geo Vigila AV, Zhang SZ, Feng SX, Liao WB. A review of the use of pteridophytes for treating human ailments. J Zhejiang Univ Sci B 2018; 19 (02) 85-119
    CrossrefPubMedSearch in Google Scholar
  • 7 Bandyopadhyay A, Dey A. Medicinal pteridophytes: ethnopharmacological, phytochemical, and clinical attributes. Beni Suef Univ J Basic Appl Sci 2022; 11 (01) 113
    CrossrefSearch in Google Scholar
  • 8 Vasänge-Tuominen M, Perera-Ivarsson P, Shen J, Bohlin L, Rolfsen W. The fern Polypodium decumanum, used in the treatment of psoriasis, and its fatty acid constituents as inhibitors of leukotriene B4 formation. Prostaglandins Leukot Essent Fatty Acids 1994; 50 (05) 279-284
    CrossrefPubMedSearch in Google Scholar
  • 9 Semwal P, Painuli S, Painuli KM. et al. Diplazium esculentum (Retz.) Sw.: ethnomedicinal, phytochemical, and pharmacological overview of the himalayan ferns. Oxid Med Cell Longev 2021; 2021: 1917890
    CrossrefPubMedSearch in Google Scholar
  • 10 Lin LJ, Huang XB, Lv ZC. Isolation and identification of flavonoids components from Pteris vittata L. Springerplus 2016; 5 (01) 1649
    CrossrefPubMedSearch in Google Scholar
  • 11 Chaturvedi M, Nagre K, Yadav JP. In silico approach for identification of natural compounds as potential COVID 19 main protease (Mpro) inhibitors. Virusdisease 2021; 32 (02) 325-329
    CrossrefPubMedSearch in Google Scholar
  • 12 Aliye M, Dekebo A, Tesso H, Abdo T, Eswaramoorthy R, Melaku Y. Molecular docking analysis and evaluation of the antibacterial and antioxidant activities of the constituents of Ocimum cufodontii . Sci Rep 2021; 11 (01) 10101
    CrossrefPubMedSearch in Google Scholar
  • 13 Azam SS, Abbasi SW. Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines. Theor Biol Med Model 2013; 10 (01) 63
    CrossrefPubMedSearch in Google Scholar
  • 14 Susmi TF, Rahman Khan MM, Rahman A. et al. In vitro antioxidant and cytotoxicity activities and in silico anticancer property of methanolic leaf extract of Leucas indica . Inform Med Unlocked 2022; 31: 100963
    CrossrefSearch in Google Scholar
  • 15 Kumari A, Singh A, Raghava M. et al. An approach of computer-aided drug design (CADD) tools for in silico assessment of various inhibitors of lanosterol-14α demethylase. Mater Today Proc 2023
    Search in Google Scholar
  • 16 Ortega MA, Fraile-Martínez O, Asúnsolo Á, Buján J, García-Honduvilla N, Coca S. Signal transduction pathways in breast cancer: the important role of PI3K/Akt/mTOR. J Oncol 2020; 2020: 9258396
    CrossrefPubMedSearch in Google Scholar
  • 17 Alamri MA, Alamri MA. Pharmacophore and docking-based sequential virtual screening for the identification of novel sigma 1 receptor ligands. Bioinformation 2019; 15 (08) 586-595
    CrossrefPubMedSearch in Google Scholar