Bioinformatics and Molecular Docking Study of Amentoflavone and 3,8-Biapigenin as Inhibitors on Cervical Cancer Proteins

Dhecella Winy Cintya Ningrum, Triana Arum Kusumaningtyas, Rifki Febriansah, Melisa Juniananda, Sri Tasminatun, Annisa Krisridwany

Abstract


Cervical cancer maintains its second-place ranking for Indonesia's highest number of cancer cases. In 2021, there were 36,633 cases of cervical cancer in Indonesia, with a rising death rate. Commonly, chemotherapy is used to treat cervical cancer and can improve the survival chances of patients, but these therapies imply increased toxicity. Biflavonoid group compounds like amentoflavone and 3,8-Biapigenin have the potential to act as anticancer agents by modulating multiple signaling pathways. This study aims to determine the cervical anticancer potential of amentoflavone and 3,8-Biapigenin based on in silico study. Prediction of anticancer activity in silico using Prediction of Activity Spectra for Active Substances (PASS) online, followed by target protein tracing using STITCH-STRING, then receptor analysis test using Ramachandran plot. A molecular docking test was conducted to determine the binding affinity of the compound with the receptor. Based on the online PASS, the compounds as thought to have low cervical anticancer potential if tested on a laboratory scale. STAT3, EP300, CYP1A1, and AKR1C1 proteins used in this study have met the requirements of a suitable receptor for molecular docking test. The best binding affinity was obtained at the interaction of amentoflavone and STAT3 with a better docking score (-9.3 kcal/mol) than doxorubicin (-7.1 kcal/mol). Overall, the results suggest biflavonoid compounds have the potential to be developed as a chemopreventive agent for cervical cancer.


Keywords: bioinformatics, molecular docking, amentoflavone, 3,8-Biapigenin, cervical cancer protein.


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References


Chelliah, D.A., 2008, Biological Activity Prediction of an Ethno Medicinal Plant Cinnamomum camphora Through Bio-informatics, Ethnobotanical Leaflets, 12, 181–190.

Cohen, P.A., Jhingran, A., Oaknin, A., and Denny, L., 2019, Cervical cancer, The Lancet., 393(10167), 169–182. CrossRef

Filimonov, D.A., Lagunin, A.A., Gloriozova, T.A., Rudik, A.V., Druzhilovskii, D.S., Pogodin, P.V., and Poroikov, V.V., 2014, Prediction of the biological activity spectra of organic compounds using the pass online web resource, Chemistry of Heterocyclic Compounds, 50(3), 444–457. CrossRef

Glowacki, E.D., Vladu, M.I., Bauer, S., and Sariciftci, N.S., 2013, Hydrogen-bonds in molecular solids-from biological systems to organic electronics, J. Mater. Chem. B., 31, 3742-3753. CrossRef

Ho, B.K., and Brasseur, R., 2005, The Ramachandran plots of glycine and pre-proline, BMC Structural Biology, 5, 1–11.

Kim, J.-K., Shin, S., Lee, J-Y., Lee, S., Lee, E., Jin, Q., et al., 2011, Biapigenin, Candidate of an Agonist of Human Peroxisome Proliferator- Activated Receptor γ with Anticancer Activity, Bulletin of the Korean Chemical Society, 32(8), 2717.

Lei, J., Wang, Y., Li, W., Fu, S., Zhou, J., Lu, D., et al., 2022, Natural green deep eutectic solvents-based eco-friendly and efficient extraction of flavonoids from Selaginella moellendorffii: Process optimization, composition identification and biological activity, Separation and Purification Technology, 283, 120203.

Maduro, J.H., Pras. E., Willemse, P..H.B., and de Vries, E.G.E., 2003, Acute and long-term toxicity following radiotherapy alone or in combination with chemotherapy for locally advanced cervical cancer, Cancer Treatment Reviews, 29(6), 471–488. CrossRef

Marcou, G. and Rognan, D., 2007, Optimizing fragment and scaffold docking by use of molecular interaction fingerprints, Journal of Chemical Information and Modeling, 47(1), 195–207. CrossRef

Masjedi, A., Hashemi, V., Hojjat-Farsangi, M., Ghalamfarsa, G., Azizi, G., Yousefi, M. and Jadidi-Niaragh, F., 2018, The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer, Biomedicine and Pharmacotherapy, 108, 1415–1424. CrossRef

Otto, S. and Engberts, J.B.F.N., 2003, Hydrophobic interactions and chemical reactivity, Organic and Biomolecular Chemistry, 1, 2809–2820. CrossRef

Puspaningtyas, A.R., 2013, Docking Molekul Dengan Metoda Molegro Virtual Docker Dari Ekstrak Air Psidium guajava, Linn Dan Citrus sinensis, Peels Sebagai Inhibitor Pada Tirosinase Untuk Pemutih Kulit, Jurnal Kimia Terapan Indonesia, 15(1), 31–39. CrossRef

Rastini, M.B.O., Giantari, N.K.M., Adnyani, K.D. and Laksmiani, N.P.L., 2019, Molecular Docking Aktivitas Antikanker Dari Kuersetin Terhadap Kanker Payudara Secara in Silico, Jurnal Kimia, 13(2), 180-184. CrossRef

Ren, W., Li, Y., Wu, S., Feng, H. and Li, R., 2016, Protein-protein interaction (PPI) network and significant gene analysis of breast cancer, International Journal of Clinical and Experimental Medicine, 9(6), 9033–9043.

Simos, T., Georgopoulou, U., Thyphronitis, G., Koskinas, J. and Papaloukas, C., 2015, Analysis of protein interaction networks for the detection of candidate hepatitis B and C biomarkers, IEEE Journal of Biomedical and Health Informatics, 19(1), 181–189. CrossRef

Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F., 2021, Global Cancer Statistics 2020 : GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA: A Cancer Journal for Clinicians, 71(3), 209–249. CrossRef

Szklarczyk, D., Santos, A., von Mering, C., Jensen, L.J., Bork, P. and Kuhn, M., 2016, STITCH 5 : augmenting protein–chemical interaction networks with tissue and affinity data, Nucleic Acids Res., 44(D1), 380–384. CrossRef

Szklarczyk, D., Gable, A.L., Lyon, D., Junge, A., Wyder, S., Huerta-Cepas, J., et al., 2019, STRING v11 : protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets, Nucleic Acids Research, 47(D1), D607-D613. CrossRef

Wang, H-Q., Man, Q-W., Huo, F-Y., Gao, X., Lin, H., Li, S-R., et al., 2022, STAT3 pathway in cancers: Past, present, and future, MedComm, 3(2), e124. CrossRef

Yu, H., Lee, H., Herrmann, A., Buettner, R. and Jove, R., 2014, Revisiting STAT3 signalling in cancer: New and unexpected biological functions, Nature Reviews Cancer., 14(11), 736–746. CrossRef

Yu, S., Yan, H., Zhang, L., Shan, M., Chen, P., Ding, A. and Li, S.F.Y., 2017, A review on the phytochemistry, pharmacology, and pharmacokinetics of amentoflavone, a naturally-occurring biflavonoid, Molecules, 22(2), 299. CrossRef

Yuliana, A., Fitriaji, S.P.H., Mukhaufillah, K.S. and Rizkuloh, L.R., 2020, In Silico Study on Testing Antidiabetic Compounds Candidate from Azaphilone Monascus sp., Microbiology Indonesia, 14(2), 52–65. CrossRef




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev14iss2pp105-116

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