In Silico Exploration of Podophyllum hexandrum-Derived phytocompounds as Potential Therapeutics against Small Cell Lung Cancer (SCLC): A Molecular Docking Approach


Notice

This is an unedited manuscript accepted for publication and provided as an Article in Press for early access at the author’s request. The article will undergo copyediting, typesetting, and galley proof review before final publication. Please be aware that errors may be identified during production that could affect the content. All legal disclaimers of the journal apply.

Year : 2025 | Volume : 03 | Issue : 01 | Page : –
    By

    Akanksha Kriti,

  1. Research Scholar, Department of Bioinformatics, BioNome Pvt Ltd, Bangalore, Karnatka, India

Abstract

document.addEventListener(‘DOMContentLoaded’,function(){frmFrontForm.scrollToID(‘frm_container_abs_176095’);});Edit Abstract & Keyword

Small Cell Lung Cancer (SCLC) is a fast-growing and aggressive type of lung cancer that spreads quickly strongly associated with smoking. It is characterized by symptoms such as persistent cough,breathing difficulties, or hoarseness, though it can sometimes be asymptomatic which makesearly detection challenging. The tumor suppressor gene TP53 is critical in regulating the cell cycle and preventing uncontrolled cell division. Mutations in TP53 result in the loss of its tumor-suppressing function, facilitating the development and progression of cancers likeSCLC. Podophyllum hexandrum (PH), a medicinal plant known for its anticancer properties, has demonstrated significant therapeutic potential in inhibiting tumor growth andprogression. PubChem is a primary resource for obtaining information and molecular structures of the phytocompounds. Various other tools were utilized to perform pharmacological assessments, particularly analyzing the ADME properties of these compounds. ProTox-II is a tool employed for toxicity prediction, ensuring the safety and efficacy of the identified compounds. This study explores the ability of phytocompounds derived from PH to target TP53 mutations in SCLC through molecular docking analysis.Molecular docking provides a computational approach to identify potential drug candidates by estimating how strongly they interact with target proteins. Using PyRx and BIOVIA, molecular.docking revealed that specific phytocompounds from PH demonstrated strong binding affinities as antagonists against mutated TP53, a key factor in SCLC progression. Thesefindings highlight the significant potential for developing effective drug candidates to target SCLC, offering a promising path for therapeutic development. This study will focus on computational drug discovery, facilitating faster drug candidate identification, cost and time reduction, and optimization prior to experimental testing.

Keywords: small cell lung cancer; podophyllum hexandrum; molecular docking; in silico analysis; TP53 gene.

[This article belongs to International Journal of Molecular Biotechnological Research (ijmbr)]

How to cite this article:
Akanksha Kriti. In Silico Exploration of Podophyllum hexandrum-Derived phytocompounds as Potential Therapeutics against Small Cell Lung Cancer (SCLC): A Molecular Docking Approach. International Journal of Molecular Biotechnological Research. 2025; 03(01):-.
How to cite this URL:
Akanksha Kriti. In Silico Exploration of Podophyllum hexandrum-Derived phytocompounds as Potential Therapeutics against Small Cell Lung Cancer (SCLC): A Molecular Docking Approach. International Journal of Molecular Biotechnological Research. 2025; 03(01):-. Available from: https://journals.stmjournals.com/ijmbr/article=2025/view=0


document.addEventListener(‘DOMContentLoaded’,function(){frmFrontForm.scrollToID(‘frm_container_ref_176095’);});Edit

References

  1. Rudin CM, Brambilla E, Faivre-Finn C, Sage J. Small-cell lung cancer. Nat Rev Dis Primers. 2021 Jan 14;7:3. doi: 10.1038/s41572-020-00231-9.
  2. Teicher BA. Targets in small cell lung cancer. Biochem Pharmacol. 2014 Jan 15;87(2):211-9. doi: 10.1016/j.bcp.2013.09.014. Epub 2013 Sep 30.
  3. Mamdani H, Induru R, Jalal SI. Novel therapies in small cell lung cancer. Transl Lung Cancer Res. 2015 Oct;4(5):533-44. doi: 10.3978/j.issn.2218-6751.2015.07.20. PMID: 26629422; PMCID: PMC4630526.
  4. Jin Y, Wu Y, Reuben A, Zhu L, Gay CM, Wu Q, et al. Single-cell and spatial proteo-transcriptomic profiling reveals immune infiltration heterogeneity associated with neuroendocrine features in small cell lung cancer. Cell Discov. 2024 Sep 4;10(1):93. doi: 10.1038/s41421-024-00703-x. PMID: 39231924; PMCID: PMC11375181.
  5. Chaudhary P, Janmeda P, Pareek A, Chuturgoon AA, Sharma R, Pareek A. Etiology of lung carcinoma and treatment through medicinal plants, marine plants and green synthesized nanoparticles: A comprehensive review. Biomed Pharmacother. 2024 Apr;173:116294. Available online: 2024 Feb 23.
  6. Wang Y, Zou S, Zhao Z, Liu P, Ke C, Xu S. New insights into small-cell lung cancer development and therapy. Cell Biol Int. 2020 Aug;44(8):1564-76. doi: 10.1002/cbin.11359. Epub 2020 Apr 18. PMID: 32281704; PMCID: PMC7496722.
  7. Zhang B, Birer SR, Dvorkin M, Shruti J, Byers L. New therapies and biomarkers: Are we ready for personalized treatment in small cell lung cancer? Am Soc Clin Oncol Educ Book. 2021 Mar;41:1-10. doi: 10.1200/EDBK_320673. PMID: 33979194.
  8. Megyesfalvi Z, Gay CM, Popper H, Pirker R, Ostoros G, Heeke S, et al. Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions. CA Cancer J Clin. 2023 Nov-Dec;73(6):620-52. doi: 10.3322/caac.21785. Epub 2023 Jun 17. PMID: 37329269.
  9. Pate SR, Das M. Small cell lung cancer: Emerging targets and strategies for precision therapy. Cancers (Basel). 2023 Aug 8;15(16):4016. doi: 10.3390/cancers15164016. PMID: 37627044; PMCID: PMC10452729.
  10. Solta A, Ernhofer B, Boettiger K, Megyesfalvi Z, Heeke S, Hoda MA, Lang C, Aigner C, Hirsch FR, Schelch K, Döme B. Small cells – big issues: biological implications and preclinical advancements in small cell lung cancer. Mol Cancer. 2024 Feb 24;23(1):41. doi: 10.1186/s12943-024-01953-9.
  11. Caliman E, Fancelli S, Petroni G, Michelet MRG, Cosso F, Ottanelli C, et al. Challenges in the treatment of small cell lung cancer in the era of immunotherapy and molecular classification. Mol Cancer. 2024 Feb 24;23(1):41. doi: 10.1186/s12943-024-01953-9. PMID: 38395864; PMCID: PMC10893629.
  12. Kumar J, Sandal P, Singh A, Kumar A, Arya V, Devi R, et al. Conservation status, anticancer compounds and pharmacological aspects of Podophyllum hexandrum Royle: A review. Indian J Ecol. 2022 Jul;49(3(SI)):1096-1102. doi: 10.55362/IJE/2022/3637.
  13. Chaurasia OP, Ballabh B, Tayade A, Kumar R, Kumar GP, Singh SB. Podophyllum: An endangered and anticancerous medicinal plant–An overview. Indian J Tradit Knowl. 2012 Apr;11(2):234-241.
  14. Anand U, Biswas P, Kumar V, Ray D, Ray P, Loake VIP, et al. Podophyllum hexandrum and its active constituents: Novel radioprotectants. Biomed Pharmacother. 2022 Feb;146:112555. doi: 10.1016/j.biopha.2021.112555. Epub 2021 Dec 23.
  15. Feng H, Chen G, Zhang Y, Guo M. Potential anti-proliferative, anti-inflammatory, and anti-viral components from Sinopodophyllum hexandrum explored using bio-affinity ultrafiltration with multiple drug targets. Biomed Pharmacother. 2022 Feb;146:112555. doi: 10.1016/j.biopha.2021.112555. Epub 2021 Dec 23.
  16. Drapkin BJ, Rudin CM. Advances in small-cell lung cancer (SCLC) translational research. Cold Spring Harb Perspect Med. 2021 Apr 1;11(4):a038240. doi: 10.1101/cshperspect.a038240. PMID: 32513672; PMCID: PMC8015694.
  17. Li M, Zhou L, Yang D, Li T, Li W. Biochemical composition and antioxidant capacity of extracts from Podophyllum hexandrum BMC Complement Altern Med. 2012 Dec 22;12:263. doi: 10.1186/1472-6882-12-263.
  18. Giri A, Narasu ML. Production of podophyllotoxin from Podophyllum hexandrum: A potential natural product for clinically useful anticancer drugs.
  19. Ekins S, Mestres J, Testa B. In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. Br J Pharmacol. 2007 Sep;152(1):9-20. doi: 10.1038/sj.bjp.0707305. Epub 2007 Jun 4. PMID: 17549047; PMCID: PMC1978274.
  20. McWilliam H, Li W, Uludag M, Squizzato S, Park YM, Buso N, et al. Analysis tool web services from the EMBL-EBI. Nucleic Acids Res. 2024;52(W1):W597–W600.
  21. BIOVIA Discovery Studio Visualizer. Version 21. San Diego, California, United States: Dassault Systèmes; 2024. p. 779.
  22. Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, et al. ADMETlab 3.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res. 2024;52(W1):W422–W430.
  23. Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-III: A webserver for predicting the toxicity of chemicals. Nucleic Acids Res. 2024;52(W1):W257–W263.
  24. Hollingsworth SA, Karplus PA. A fresh look at the Ramachandran plot and the occurrence of standard structures in proteins. Biomol Concepts. 2010 Oct;1(3-4):271–283. doi: 10.1515/BMC.2010.022. Available in PMC: 2011 Oct 1. PMCID: PMC3061398. NIHMSID: NIHMS231707. PMID: 21436958.
  25. Agu PC, Afiukwa CA, Orji OU, Ezeh EM, Ofoke IH, Ogbu CO, Ugwuja EI, Aja PM. Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in disease management. Sci Rep. 2023 Aug 17;13:13398. doi: 10.1038/s41598-023-39923-4.
  26. Srivastava U, Sood H. Propagation of Podophyllum hexandrum Royale to enhance production of podophyllotoxin. In: IntechOpen; 2020 Oct 7. doi: 10.5772/intechopen.93704.
  27. Sharma A, Sharma P. The Himalayan May Apple (Podophyllum hexandrum): A review. Himachal Pradesh State Biodiversity Board. Published: 23 Nov 2018. Received: 21 Oct 2018; Accepted: 15 Nov 2018.
  28. Hidding BI, Raskin J, Janssens A. Recent developments in the treatment of small cell lung cancer. Eur Respir Rev. 2021;30(161):210079. doi: 10.1183/16000617.0079-2021.
  29. Farago AF, Keane FK. Current standards for clinical management of small cell lung cancer. Transl Lung Cancer Res. 2018 Feb 15;7(1):1-8. doi: 10.21037/tlcr.2018.01.16. Submitted: Nov 16, 2017; Accepted: Jan 26, 2018.
  30. Yang S, Zhang Z, Wang Q. Emerging therapies for small cell lung cancer. J Hematol Oncol. 2019 May 2;12:47. doi: 10.1186/s13045-019-0737-5.
Regular Issue Subscription Original Research
Volume 03
Issue 01
Received 27/12/2024
Accepted 07/02/2025
Published 28/02/2025
Publication Time 63 Days
207

async function fetchCitationCount(doi) {
let apiUrl = `https://api.crossref.org/works/${doi}`;
try {
let response = await fetch(apiUrl);
let data = await response.json();
let citationCount = data.message[“is-referenced-by-count”];
document.getElementById(“citation-count”).innerText = `Citations: ${citationCount}`;
} catch (error) {
console.error(“Error fetching citation count:”, error);
document.getElementById(“citation-count”).innerText = “Citations: Data unavailable”;
}
}
fetchCitationCount(“10.1037/ppm0000185”);

10.37591/IJMBR.v03i01.0

Loading citations…