Molecular Docking and ADMET Study of Phytochemicals as Anticancer Agent towards Alpha 1- Antichymotrypsin Variant DBS-II and Oxidised Quinone Reductase-2

Pallavi Patil *

P.E.S’ Modern College of Pharmacy, Nigdi, Pune-411044, India.

Neha Shegokar

P.E.S’ Modern College of Pharmacy, Nigdi, Pune-411044, India.

Pratiksha Raut

P.E.S’ Modern College of Pharmacy, Nigdi, Pune-411044, India.

Aditya Chonde

P.E.S’ Modern College of Pharmacy, Nigdi, Pune-411044, India.

*Author to whom correspondence should be addressed.


Abstract

Objective: The main goals of this study were to do molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) tests on vanillic acid, ferulic acid, chlorogenic acid, and catechin hydrate. The study aimed to determine the receptor affinity of these drugs using molecular docking simulations, with a focus on the potential anticancer impact of targeting the Alpha 1-Antichymotrypsin Variant DBS-II and Oxidised Quinone Reductase-2.

Materials and Methods: Doxorubicin was used as a reference standard for the molecular docking investigations of the compounds, which were performed using Protein Data Bank (PDB) ID: 4ZVM and PDB ID 5OM7. Additionally, we performed ADMET investigations of these drugs using SwissADME and ProTox-II software programmes.

Results: Chlorogenic acid exhibited a higher score than the other three compounds with regard to anticancer activity, with scores of -7.869 Kcal/mole for oxidised quinone reductase-2 in complex and -5.941 Kcal/mole for Alpha1-Antichymotrypsin Variant DBS-II, respectively, after the reference drug. ADMET analysis demonstrated the suitability of these compounds for use in pharmaceutical applications.

Conclusion: Studies show that all four drugs bind to Oxidised Quinone Reductase-2 (OQR-2) and Alpha 1-Antichymotrypsin Variant DBS-II, which could mean that they can fight cancer. In addition, the toxicity evaluation and ADME analysis reveal how suitable these substances are for use in pharmaceuticals.

Keywords: Anticancer activity, alpha 1-antichymotrypsin variant DBS-II, oxidised quinone reductase-2, molecular docking, ADMET properties


How to Cite

Patil , P., Shegokar, N., Raut, P., & Chonde , A. (2024). Molecular Docking and ADMET Study of Phytochemicals as Anticancer Agent towards Alpha 1- Antichymotrypsin Variant DBS-II and Oxidised Quinone Reductase-2. UTTAR PRADESH JOURNAL OF ZOOLOGY, 45(11), 38–49. https://doi.org/10.56557/upjoz/2024/v45i114068

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References

Fouad YA, Aanei C. Revisiting the hallmarks of cancer. American Journal of Cancer Research. 2017;7(5):1016.

National Cancer Institute. PDQ® Adult Treatment Editorial Board. PDQ Adult Acute Lymphoblastic Leukemia Treatment. Bethesda, MD; 2020. Available:https://www.cancer.gov/types/leukemia/patient/adult-all-treatment-pdq

Yang JS, Liu CW, Ma YS, Weng SW, Tang NY, Wu SH, Ji BC, Ma CY, Ko YC, Funayama S, Kuo CL. Chlorogenic acid induces apoptotic cell death in U937 leukemia cells through caspase-and mitochondria-dependent pathways. In vivo. 2012;26(6):971-8.

Novellasdemunt L, Antas P, Li VSW. Targeting WNT signaling in colorectal cancer. A Review in the Theme: Cell Signaling: Proteins, Pathways and Mechanisms. Am J Physiol Cell Physiol. 2015;309(8):C511–21. Available:https://pubmed.ncbi.nlm.nih.gov/26289750/

Cheng X, Xu X, Chen D, Zhao F, Wang W. Therapeutic potential of targeting the Wnt/β-catenin signaling pathway in colorectal cancer. Biomedicine and Pharmacotherapy. 2019;110:473–81.

Zhai Y, Wang T, Fu Y, Yu T, Ding Y, Nie H. Ferulic acid: A review of pharmacology, toxicology, and therapeutic effects on pulmonary diseases. International Journal of Molecular Sciences. 2023;24:8011 Available:https://www.mdpi.com/1422-0067/24/9/8011/htm

Park J, Cho SY, Kang J, Park WY, Lee S, Jung Y, et al. Vanillic acid improves comorbidity of cancer and obesity through stat3 regulation in high-fat-diet-induced obese and B16bl6 melanoma-injected mice. Biomolecules. 2020;10(8):1–18. Available:/pmc/articles/PMC7464557/

Gong J, Zhou S, Yang S. Vanillic acid suppresses HIF-1α Expression via Inhibition of mTOR/p70S6K/4E-BP1 and Raf/MEK/ERK Pathways in Human Colon Cancer HCT116 Cells. Int J Mol Sci [Internet]. 2019;20(3).

Available:https://pubmed.ncbi.nlm.nih.gov/30678221/

Khan N, Afaq F, Saleem M, Ahmad N, Mukhtar H. Targeting Multiple Signaling Pathways by Green Tea Polyphenol (−)-Epigallocatechin-3-Gallate. Cancer Res. 2006;66(5):2500–5.

Available:/cancerres/article/66/5/2500/526677/Targeting-Multiple-Signaling-Pathways-by-Green-Tea

Dinkova-Kostova AT, Talalay P. NAD (P) H: Quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector. Arch Biochem Biophys [Internet]. 2010;501(1):116. Available:/pmc/articles/PMC2930038/

Adegbesan BO. Investigation of the anti-cancer properties of natural products and synthetic analogues with nqo2 inhibiting potential.

The potential role of the oxidoreductase, NQO2 in breast cancer Elham Santina; 2015.

Ikhmais BAJ. The Role of NQO2 in Tumour Growth and Response to Therapeutic Drugs; 2017.

De Sá Junior PL, Câmara DAD, Porcacchia AS, Fonseca PMM, Jorge SD, Araldi RP, et al. The Roles of ROS in Cancer Heterogeneity and Therapy. Oxid Med Cell Longev. 2017;2017.

Nimal R, Selcuk O, Kurbanoglu S, Shah A, Siddiq M, Uslu B. Trends in electrochemical nanosensors for the analysis of antioxidants. TrAC Trends in Analytical Chemistry. 2022;153:116626.

Gardill BR, Schmidt K, Muller YA. NewBG: A surrogate corticosteroid-binding globulin with an unprecedentedly high ligand release efficacy. J Struct Biol [Internet]. 2019;207(2):169–82.

Available:https://pubmed.ncbi.nlm.nih.gov/31103428/

Schmidt K, Gardill BR, Kern A, Kirchweger P, Börsch M, Muller YA. Design of an allosterically modulated doxycycline and doxorubicin drug-binding protein. Proc Natl Acad Sci USA. 2018;115(22):5744–9. Available:https://www.pnas.org/doi/abs/10.1073/pnas.1716666115

Kalsheker NA. Alpha 1-antichymotrypsin. Int J Biochem Cell Biol. 1996;28(9):961–4.

Available:https://pubmed.ncbi.nlm.nih.gov/8930118/

Bond JS. Proteases: History, discovery, and roles in health and disease. Journal of Biological Chemistry. 2019; 294(5): 1643– 51. Available:http://www.jbc.org/article/S0021925820364772/fulltext