DESIGN OF QUINOLINE-CHALCONE HYBRIDS DERIVATIVES AS ANTICANCER USING QSAR AND MOLECULAR DOCKING STUDIES
Abstract
Cancer is a disease caused by abnormal growth of cells that has infected many people in the world. This reason encourages many scientists to conduct research on the development of medicinal compounds as cancer therapy. One of the drugs that has the potential to be developed is based on the quinone-chalcone structure. One method of drug development to obtain high effectiveness is to use the Quantitative Structure-Activity Relationship (QSAR) method. In this study, QSAR problem modelling was developed for quinone-chalcone derivative compounds that have been synthesized previously. Some parameters (descriptors) used in this study were obtained from quantum mechanical modelling with AM1 and ZINDO/S semiempirical methods. The relationship between descriptors and anticancer activity (pIC50) was obtained using the Multiple Linear Regression (MLR) method, so that the QSAR model equation pIC50 = -6.39 + 0.17(binding) - 1.87(LUMO) - 9.29(qC2) + 9.67(qC1) - 41.02(qC5) – 9.86(qC14) + 6.94(qC18) was obtained. This equation has a value of R = 0.998 with Sig = 0.017, therefore it can be said that the equation is valid and represents the relationship between descriptors and pIC50. Based on the QSAR equation, four new compound designs were proposed and tested using molecular docking. The results of pIC50 prediction and molecular docking showed that compound design 12 has the best potential as an anticancer compound.
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References
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Álvarez, R., Aramburu, L., Puebla, P., Caballero, E., González, M., Vicente, A., Medarde, M., & Peláez, R. (2016). Pyridine Based Antitumour Compounds Acting at the Colchicine Site. Current Medicinal Chemistry, 23(11), 1100–1130. https://doi.org/10.2174/092986732311160420104823
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Hari Narayana Moorthy, N. S., Ramos, M. J., & Fernandes, P. A. (2011). Topological, hydrophobicity, and other descriptors on α-glucosidase inhibition: a QSAR study on xanthone derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry, 26(6), 755–766. https://doi.org/10.3109/14756366.2010.549089
Hou, Q., Lin, X., Lu, X., Bai, C., Wei, H., Luo, G., & Xiang, H. (2020). Discovery of novel steroidal-chalcone hybrids with potent and selective activity against triple-negative breast cancer. Bioorganic and Medicinal Chemistry, 28(23). https://doi.org/10.1016/j.bmc.2020.115763
Li, W., Sun, H., Xu, S., Zhu, Z., & Xu, J. (2017). Tubulin inhibitors targeting the colchicine binding site: a perspective of privileged structures. Future Medicinal Chemistry, 9(15), 1765–1794. https://doi.org/10.4155/fmc-2017-0100
Love, R. R., Young, G. S., Laudico, A. V., Van Dinh, N., Uy, G. B., Quang, L. H., De La Peña, A. S., Dofitas, R. B., Bisquera, O. C., Siguan, S. S. S., Salvador, J. D. S., Mirasol-Lumague, M. R., Navarro, N. S., Linh, N. D., & Jarjoura, D. (2013). Bone mineral density following surgical oophorectomy and tamoxifen adjuvant therapy for breast cancer. Cancer, 119(21), 3746–3752. https://doi.org/10.1002/cncr.28302
Luo, Y., Wu, W., Zha, D., Zhou, W., Wang, C., Huang, J., Chen, S., Yu, L., Li, Y., Huang, Q., Zhang, J., & Zhang, C. (2021). Synthesis and biological evaluation of novel ligustrazine-chalcone derivatives as potential anti-triple negative breast cancer agents. Bioorganic and Medicinal Chemistry Letters, 47. https://doi.org/10.1016/j.bmcl.2021.128230
Mirzaei, S., Hadizadeh, F., Eisvand, F., Mosaffa, F., & Ghodsi, R. (2020). Synthesis, structure-activity relationship and molecular docking studies of novel quinoline-chalcone hybrids as potential anticancer agents and tubulin inhibitors. Journal of Molecular Structure, 1202. https://doi.org/10.1016/j.molstruc.2019.127310
Moore, J., Yousef, M., & Tsiani, E. (2016). Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols. Nutrients, 8(11), 731. https://doi.org/10.3390/nu8110731
Su, Q.-G., Liu, Y., Cai, Y.-C., Sun, Y.-L., Wang, B., & Xian, L.-J. (2011). Anti-tumour effects of xanthone derivatives and the possible mechanisms of action. Investigational New Drugs, 29(6), 1230–1240. https://doi.org/10.1007/s10637-010-9468-5
Syahri, J., Hidayah, N., Hilma, R., Nurohmah, B. A., & Yuanita, E. (2020). Design of New 2,4-Substituted Furo [3,2-B] Indole Derivatives as Anticancer Compounds Using Quantitative Structure-Activity Relationship (QSAR) and Molecular Docking. Molekul, 15(1), 9. https://doi.org/10.20884/1.jm.2020.15.1.582
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Trott, O., & Olson, A. J. (2009). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, NA-NA. https://doi.org/10.1002/jcc.21334
Tseng, C.-H., Tzeng, C.-C., Hsu, C.-Y., Cheng, C.-M., Yang, C.-N., & Chen, Y.-L. (2015). Discovery of 3-phenylquinolinylchalcone derivatives as potent and selective anticancer agents against breast cancers. European Journal of Medicinal Chemistry, 97, 306–319. https://doi.org/10.1016/j.ejmech.2015.04.054
World Health Organization. (2022, February 3). Cancer. Https://Www.Who.Int/News-Room/Fact-Sheets/Detail/Cancer.
Yakes, F. M., Chen, J., Tan, J., Yamaguchi, K., Shi, Y., Yu, P., Qian, F., Chu, F., Bentzien, F., Cancilla, B., Orf, J., You, A., Laird, A. D., Engst, S., Lee, L., Lesch, J., Chou, Y.-C., & Joly, A. H. (2011). Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Molecular Cancer Therapeutics, 10(12), 2298–2308. https://doi.org/10.1158/1535-7163.MCT-11-0264
Zhang, E.-H., Wang, R.-F., Guo, S.-Z., & Liu, B. (2013). An Update on Antitumor Activity of Naturally Occurring Chalcones. Evidence-Based Complementary and Alternative Medicine, 2013, 1–22. https://doi.org/10.1155/2013/815621
Published
2025-02-01
How to Cite
ARIEFIN, Mokhamat et al.
DESIGN OF QUINOLINE-CHALCONE HYBRIDS DERIVATIVES AS ANTICANCER USING QSAR AND MOLECULAR DOCKING STUDIES.
Jurnal Kimia (Journal of Chemistry), [S.l.], feb. 2025.
ISSN 2599-2740.
Available at: <https://ojs.unud.ac.id/index.php/jchem/article/view/107934>. Date accessed: 07 feb. 2025.
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Articles
This work is licensed under a Creative Commons Attribution 4.0 International License
