Molecular Docking and ADMET-Based Screening of Natural Plant Hormones as Potential MMP9 Inhibitors in Cervical Cancer
DOI:
https://doi.org/10.31580/pjmls.v9i2.3428Keywords:
Cervical cancer, MMP9, Molecular docking, Phytochemicals, Luteolin, ADMET analysisAbstract
Cervical cancer is a significant health problem due to late diagnosis and poor treatment, resulting in an increasing death rate each year. This malignancy is caused by a variety of hereditary variables, and matrix metalloproteinase-9 (MMP9) is a crucial protein that contributes to extracellular matrix breakdown, tumor invasion, and metastasis, making it a possible target for therapeutic drugs. This research involved an in silico study to identify essential plant hormones as natural inhibitors against MMP9. This protein's FASTA sequence was obtained from the NCBI database, and GOR I, AlphaFold, and Procheck were used to perform additional structure prediction analysis. ExPASy ProtParam and TMHMM tools were employed to examine physicochemical and transmembrane properties of the protein. The strongest anti-cancer drugs were identified through molecular docking using PyRx and CB Dock2, which were downloaded from the PubChem database. Among these substances, luteolin, curcumin, quercetin, resveratrol, and epigallocatechin gallate, luteolin had the strongest hydrogen bond interactions with the target protein and the highest binding energy of -9.5 kcal/mol. Luteolin's pharmacokinetic characteristics were examined using further ADMET analysis, which showed that it is a promising therapeutic candidate. Finally, a safety assessment was conducted using Protox II for toxicity analysis. Consequently, luteolin has demonstrated an effective natural inhibitor of MMP9, warranting further experimental validation for its potential application in the management of cervical cancer.
References
1. Tewari KS. Cervical cancer. New England Journal of Medicine. 2025 Jan 2;392(1):56-71.
2. Xu M, Cao C, Wu P, Huang X, Ma D. Advances in cervical cancer: current insights and future directions. Cancer Communications. 2025 Feb;45(2):77-109.
3. Chen Y, Yan Y, Wei W. Research advances of matrix metalloproteinases family in uveal melanoma. European Journal of Medical Research. 2025 Jul 9;30(1):609.
4. Mbodi L, Maringa VD, Moroeng MW, Bassa S, Kaufmann AM, Dlamini Z. An overview of cervical cancer, chemotherapy as treatment and chemotherapy resistance. Strategies for Overcoming Chemotherapy Resistance in Cervical Cancer. 2024 Jan 1:1-6.
5. Yadav N, Parveen S, Banerjee M. Potential of nano-phytochemicals in cervical cancer therapy. Clinica chimica acta. 2020 Jun 1;505:60-72.
6. Sayers EW, Beck J, Bolton EE, Bourexis D, Brister JR, Canese K, Comeau DC, Funk K, Kim S, Klimke W, Marchler-Bauer A. Database resources of the national center for biotechnology information. Nucleic acids research. 2021 Jan 8;49(D1):D10-7.
7. Eskandari A, Leow TC, Rahman MB, Oslan SN. Structural investigation, computational analysis, and theoretical cryoprotectant approach of antifreeze protein type IV mutants. European Biophysics Journal. 2024 Nov;53(7):385-403.
8. Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, Tunyasuvunakool K, Bates R, Žídek A, Potapenko A, Bridgland A. Highly accurate protein structure prediction with AlphaFold. nature. 2021 Aug 26;596(7873):583-9.
9. Azimi R, Ozgul M, Kenney MC, Kuppermann BD. Bioinformatic analysis of small humanin like peptides using AlfaFold-2 and Expasy ProtParam. Investigative Ophthalmology & Visual Science. 2024 Jun 17;65(7):1320-.
10. Varghese J, Georrge JJ. An in silico approach for function prediction of hypothetical proteins of Listeria monocytogenes. InProceedings of the National Conference on Innovations in Biological Sciences (NCIBS) 2020 Apr 12.
11. Marbán-González A, Ramírez-Cid V, Cristóbal-Ramírez A, Medina-Franco JL. Exploiting PubChem and other public databases for virtual screening in 2025: what are the latest trends?. Expert Opinion on Drug Discovery. 2025 Nov 2;20(11):1387-403.
12. Tao Y, Ran B, Wang J, Hu Q, Wen Y, Qiu Q, Niu T. Exploring the potential toxic mechanisms of bisphenol F exposure in acute myeloid leukemia: Insights from network toxicology, molecular docking and experimental validation. International Immunopharmacology. 2025 Dec 3;166:115579.
13. Banerjee P, Ulker O, Ozkan I, Ulker OC. The investigation of the toxicity of organophosphorus flame retardants (OPFRs) by using in silico toxicity prediction platform ProTox-3.0. Toxicology Mechanisms and Methods. 2025 Jan 2;35(1):32-42.
14. Tshiluka NR, Mbedzi DT, Bvumbi MV, Mnyakeni‐Moleele SS. In vitro α–Glucosidase Inhibition, Cytotoxicity, SAR, Swiss ADME Prediction and Molecular Docking Study of New N–Substituted Hydantoin Derivatives. ChemistryOpen. 2025 Apr;14(4):e202400119.
15. Wang Y, Qi C, Hao M. Development of a prognostic model for cervical cancer based on inflammation-related gene signatures and immune microenvironment regulation. American Journal of Cancer Research. 2025 Sep 15;15(9):3933.
16. Canakdag M, Feizi-Dehnayebi M, Kundu S, Sahin D, İlhan İÖ, Alhag SK, Al-Shuraym LA, Akkoc S. Comprehensive evaluation of purine analogues: Cytotoxic and antioxidant activities, enzyme inhibition, DFT insights, and molecular docking analysis. Journal of Molecular Structure. 2025 Feb 25;1323:140798.
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Pak-Euro Journal of Medical and Life Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
