Molecular docking analysis between anti-apoptosis EGFR and four coumarins, and four carbazole alkaloids: in silico study

Dhona Afriza, Wastuti Hidayati Suriyah, Solachuddin Jauhari Arief Ichwan, Joe Knights

Abstract


Introduction: The anti-apoptotic protein EGFR is typically overexpressed in the majority of head and neck squamous cell carcinomas (HNSCC) and has been targeted for genetic therapy. The Clausena excavata plant is an evergreen shrub that has been widely used for various disease therapies, including cancer. Coumarin and carbazole alkaloids are the plant's primary active ingredients. This study aims to determine the molecular interaction between EGFR and several coumarins (clauslactone E, dentatin, nordentatin, clausenidin) and carbazole alkaloids (7- hydroxyheptaphylline, clausine E, 2,7 - dimethoxy - 9H - carbazole - 3- carbaldehyde,and 2,7 – dimethoxy - 9H - carbazole – 3-carboxylic acid). Methods: This research was carried out in silico using the molecular docking method. Molecular docking analysis was performed using AutoDock Vina, AutoDockTools 1.5.6., Pymol, and Discovery Studio Biovia 2021. The three-dimensional structure of the EGFR protein was retrieved from the RCSB Protein Data Bank. Ligands were obtained from the PubChem Compound Database. The comparison ligand was doxorubicin. Molecular docking results were analyzed based on binding affinity, amino acid interactions, visualization of docking results, and Lipinski's rule of five. Results: All of the investigated ligands with the EGFR receptor had strong binding affinity (-6.8 and -8.3 kcal/mol), almost the same as the comparison ligand (-8.2 kcal/mol). Each interaction also produced a different number of amino acid residues. Conclusion: These four coumarin compounds and four carbazole alkaloid compounds are considered potential EGFR inhibitors and anticancer candidates.

Keyword

Molecular docking, anticancer, oncogene protein, natural compunds


Keywords


Molecular docking, anticancer, oncogene protein, natural compunds

Full Text:

PDF

References


Kaczanowski S. Apoptosis: its origin, history, maintenance and the medical implications for cancer and aging. Phys Biol. 2016;13(3):031001. DOI:10.1088/1478-3975/13/3/031001

Neophytou CM, Trougakos IP, Erin N, Papageorgis P. Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance. Cancers (Basel). 2021;13(17):4363. DOI:10.3390/cancers13174363

Pfeffer CM, Singh ATK. Apoptosis: A Target for Anticancer Therapy. Int J Mol Sci. 2018;19(2):448. Published 2018 Feb 2. DOI:10.3390/ijms19020448

Ribeiro FA, Noguti J, Oshima CT, Ribeiro DA. Effective targeting of the epidermal growth factor receptor (EGFR) for treating oral cancer: a promising approach. Anticancer Res. 2014;34(4):1547-1552

Alsahafi E, Begg K, Amelio I, et al. Clinical update on head and neck cancer: molecular biology and ongoing challenges. Cell Death Dis. 2019;10(8):540. DOI:10.1038/s41419-019-1769-9

Vatte C, Al Amri AM, Cyrus C, et al. Tyrosine kinase domain mutations of EGFR gene in head and neck squamous cell carcinoma. Onco Targets Ther. 2017;10:1527-1533. DOI:10.2147/OTT.S132187

Fasano M, Della Corte CM, Viscardi G, Di Liello, R., Paragliola, F., Sparano, F et al. Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy. Ther Adv Med Oncol. 2021;13: 1758835920949418. DOI:10.1177/1758835920949418

Nair S, Bonner JA, Bredel M. EGFR Mutations in Head and Neck Squamous Cell Carcinoma. Int J Mol Sci. 2022;23(7):3818. DOI:10.3390/ijms23073818

Kordbacheh F, Farah CS. Current and Emerging Molecular Therapies for Head and Neck Squamous Cell Carcinoma. Cancers (Basel). 2021;13(21):5471. DOI:10.3390/cancers13215471.

Afriza, A., Orienty, FN., Ayu, WP. Molecular Docking Analysis of the Interactions between MMP-9 Protein and Four Coumarin Compounds (Nordentatin, Dentatin, Calusenidin and Xanthoxyletin). J of Int Dent and Medical Research. 2020, 13(4); 1286-1292.

Thant, T., Aminah, N., Kristanti, A., Ramadhan, R., Aung H., and Takaya, Y., Cytotoxic Carbazole Alkaloid from the Root of Clausena excavata on Hela Cell Line. In Proceedings of the 1st International Conference on Chemical Science and Technology Innovation (ICOCSTI 2019), 2020, pp141-144.

Peh TH, Lim GK, Taufiq-Yap, YH, Cheng G and Ee L. A New Cytotoxic Carbazole Alkaloid Isolated from the Stem Bark of Malaysian Clausena excavata. Can Chem Trans., 2013, 1 (3):165–172.

Albaayit SFA, Maharjan R, Abdullah R, Noor MHM. Anti-Enterococcus Faecalis, Cytotoxicity, Phytotoxicity, and Anticancer Studies on Clausena excavata Burum. f. (Rutaceae) Leaves. Biomed Res Int. 2021;2021:3123476. DOI:10.1155/2021/3123476

Afriza D, Ichwan SJA, Wahyuni FS, Suriyah WH, Yanwirasti, Tejo BA. Prediction on Binding Affinity of Nordentatin and Quercetin Against Anti-apoptotic BCL-2 Protein. J Int Dent Med Res 2018; 11(3): 1116-1122

Afriza D, Suriyah WH and Ichwan SJA. In silico analysis of molecular interactions between the anti-apoptotic protein survivin and dentatin, nordentatin, and quercetin. J. Phys.: Conf. Ser. 1073 032001.

Atkovska K, Samsonov SA, Paszkowski-Rogacz M, Pisabarro MT. Multipose binding in molecular docking. Int J Mol Sci. 2014;15(2):2622-2645. DOI:10.3390/ijms15022622

Forli S, Huey R, Pique ME, Sanner MF, Goodsell DS, Olson AJ. Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nat Protoc. 2016;11(5):905-919. DOI:10.1038/nprot.2016.051

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 diseases management. Sci Rep. 2023 Aug 17;13(1):13398. DOI: 10.1038/s41598-023-40160-2.

Karthik, D. Prediction on Binding affinity of some selected Coumarin and Anthraquinone Derivatives on Cysteine Rich C1 Domain of Kinase Suppressor of RAS- 1 (KSR-1) of MAPK signaling pathway. J of Computational Methods in Molecular Design, 2014, 4(4),131–139.

Benet LZ, Hosey CM, Ursu O, Oprea TI. BDDCS, the Rule of 5 and drugability. Adv Drug Deliv Rev. 2016;101:89-98. DOI:10.1016/j.addr.2016.05.007

Jaghoori, M. M., Bleijlevens, B., Olabarriaga, S. D., 1001 Ways to run AutoDock Vina for virtual screening. J Comput Aided Mol Des., 2016, 30(3), 237-49.

Cosconati S, Forli S, Perryman AL, Harris R, Goodsell DS, Olson AJ. Virtual Screening with AutoDock: Theory and Practice. Expert Opin Drug Discov., 2010, 5(6), 597-607.

Tallei TE, Tumilaar SG, Niode NJ, Fatimawali, Kepel BJ, Idroes R, et al., Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study. Scientifica, 2020,p 18.

Kumalo HM, Bhakat S, Soliman ME. Theory and applications of covalent docking in drug discovery: merits and pitfalls. Molecules. 2015;20(2):1984-2000. DOI:10.3390/molecules20021984

Torres PHM, Sodero ACR, Jofily P, Silva-Jr FP. Key Topics in Molecular Docking for Drug Design. Int J Mol Sci. 2019, 20(18), 4574.

Sergeev YV, Dolinska MB, and Wingfield PT. Thermodynamic analysis of weak protein interactions using sedimentation equilibrium. Curr Protoc Protein Sci., 2014, 77, 20.13.1-20.13.15.

Xiao F, Chen Z, Wei Z, Tian L. Hydrophobic Interaction: A Promising Driving Force for the Biomedical Applications of Nucleic Acids. Adv Sci (Weinh). 2020;7(16):2001048. DOI:10.1002/advs.202001048

Zhu C, Gao Y, Li H, Meng S, Li L, Francisco JS and Zeng XC. Characterizing hydrophobicity of amino acid side chains in a protein environment via measuring contact angle of a water nanodroplet on planar peptide network. Proc Natl Acad Sci USA, 2016, 113(46),12946-12951.

Quiroga R. and Villarreal MA. Vinardo: A Scoring Function Based on Autodock Vina Improves Scoring, Docking, and Virtual Screening. PLoS One. 2016, 11(5), e0155183.

Guedes IA, Pereira FSS, Dardenne LE. Empirical Scoring Functions for Structure-Based Virtual Screening: Applications, Critical Aspects, and Challenges. Front Pharmacol. 2018;9:1089. DOI:10.3389/fphar.2018.01089

Macari G, Toti D, Pasquadibisceglie A, Polticelli F. DockingApp RF: A State-of-the-Art Novel Scoring Function for Molecular Docking in a User-Friendly Interface to AutoDock Vina. Int J Mol Sci. 2020;21(24):9548.DOI :10.3390/ijms21249548

Du X, Li Y, Xia YL, Ai SM, Liang J, Sang P, Ji XL and Liu SQ. Insights into Protein-Ligand Interactions: Mechanisms, Models, and Methods. Int J Mol Sci., 2016, 17(2),144.

Muthu, S. and Durairaj, B., Molecular docking studies on interaction of Annona Muricata compounds with antiapoptotic proteins BCL-2 and survivin. Sky J Biochem Res. 2016. 5(2), 014-017.

Maksimenko A, Dosio F, Mougin J, Ferrero A, Wack S, Reddy LH, et al. A unique squalenoylated and nonpegylated doxorubicin nanomedicine with systemic long-circulating properties and anticancer activity. Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):E217-26. DOI: 10.1073/pnas.1313459110.

Dornfeld K, Madden M, Skildum A, Wallace KB. Aspartate facilitates mitochondrial function, growth arrest and survival during doxorubicin exposure. Cell Cycle. 2015;14(20):3282-91. DOI: 10.1080/15384101.2015.1087619.

Wei L, Surma M, Gough G, Shi S, Lambert-Cheatham N, Chang J, et al. Dissecting the Mechanisms of Doxorubicin and Oxidative Stress-Induced Cytotoxicity: The Involvement of Actin Cytoskeleton and ROCK1. PLoS One. 2015 Jul 2;10(7):e0131763. DOI: 10.1371/journal.pone.0131763.

Chagas CM, Moss S, Alisaraie L. Drug metabolites and their effects on the development of adverse reactions: Revisiting Lipinski’s Rule of Five. International Journal of Pharmaceutics. 2018; 549(1-2): 133-149. DOI:10.1016/j.ijpharm.2018.07.046.

Ajaykumar, C. Overview on the Side Effects of Doxorubicin. Advances in Precision Medicine Oncology. IntechOpen. 2021. Crossref, DOI:10.5772/intechopen.94896.

Sigismund S, Avanzato D, Lanzetti L. Emerging functions of the EGFR in cancer. Mol Oncol. 2018;12(1):3-20. DOI:10.1002/1878-0261.12155.

Jeong MS, Lee KW, Choi YJ, et al. Synergistic Antitumor Activity of SH003 and Docetaxel via EGFR Signaling Inhibition in Non-Small Cell Lung Cancer. Int J Mol Sci. 2021;22(16):8405. Published 2021 Aug 5. DOI:10.3390/ijms22168405.

Palumbo C, Benvenuto M, Focaccetti C, et al. Recent findings on the impact of ErbB receptors status on prognosis and therapy of head and neck squamous cell carcinoma. Front Med (Lausanne). 2023 ;10:1066021. DOI:10.3389/fmed.2023.1066021.




DOI: https://doi.org/10.24198/pjd.vol36no1.52467

Refbacks

  • There are currently no refbacks.


Visitor Stat

Creative Commons License
Padjadjaran Journal of Dentistry is licensed under Creative Commons Attribution 4.0 International License