Evaluation of the interaction of diosgenin and its derivatives with cyclodextrin to form a water-soluble inclusion complex: A molecular docking study
##plugins.themes.academic_pro.article.main##
Abstract
Diosgenin as an herbal compound has been shown to have activity as an atherosclerosis agent, but the low solubility of the compound may hinder the research process of diosgenin as a medicinal substance. This study aimed to examine the interaction and affinity of diosgenin compounds and their derivatives with the macromolecule cyclodextrin to increase solubility by inclusion complex formation. Alpha and beta cyclodextrins and all ligands were optimized using the density functional theory (DFT) method and the 6-31G base set with hybrid functional B3LYP. Next, molecular docking was carried out using AutoDock. Of the 12 compounds that were tethered to each macromolecule, the compound 2-chloro-3-(((4S,5'R,6aR,6bS,8aS,8bR,9S,10R,11aS,12aS,12bS)-5',6a,8a,9- tetramethyl-1,3,3',4,4',5,5',6,6a,6b,6',7,8,8a,8b,9,11a,12,12a,12b-icosahydrospiro[naphtho[2',1':4,5]indeno[2,1-b]furan-10,2'-pyran]-4-yl)oxy)naphthalene-1,4-dione (M18) and the α-cyclodextrins were found to have the lowest binding free energy (∆G) and inhibition constant (Ki) of -6.42 kcal/mol and 19.80 uM, respectively. The results of this study can be studied and continued as future research material to develop evidence of increasing solubility in compounds by forming inclusion complexes with macromolecules. In conclusion, diosgenin and cyclodextrin macromolecules interact to form a water-soluble inclusion complex.
##plugins.themes.academic_pro.article.details##
How to Cite
Rismawanti, R., Asnawi, A. and Muttaqin, F. Z. (2024) “Evaluation of the interaction of diosgenin and its derivatives with cyclodextrin to form a water-soluble inclusion complex: A molecular docking study”, Science Midwifery, 12(3), pp. 1206-1214. doi: 10.35335/midwifery.v12i3.1634.
References
Asnawi, A., Febrina, E., Aligita, W., Aman, L. O., & Razi, F. (2024). Molecular docking and molecular dynamics study of 3-hydroxybutyrate with polymers for diabetic ketoacidosis-targeted molecularly imprinted polymers. Journal of Pharmacy and Pharmacognosy Research, 12(5), 822–836. https://doi.org/10.56499/jppres23.1926_12.5.822
Asnawi, A., Febrina, E., Aligita, W., Yuliantini, A., & Arfan, A. (2023). Penambatan Molekul dan Dinamika Molekul beberapa Fitokimia dari Acalypha Indica L. sebagai Inhibitor Matriks Metalloproteinase9. Jurnal Sains Farmasi & Klinis, 10(1), 62. https://doi.org/10.25077/jsfk.10.1.62-70.2023
Aumsuwan, P., Khan, S. I., Khan, I. A., Ali, Z., Avula, B., Walker, L. A., Shariat-Madar, Z., Helferich, W. G., Katzenellenbogen, B. S., & Dasmahapatra, A. K. (2016). The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro. Archives of Biochemistry and Biophysics, 591, 98–110. https://doi.org/10.1016/j.abb.2015.12.001
Barkat, Md. A., Goyal, A., Barkat, H. A., Salauddin, M., Pottoo, F. H., & Anwer, E. T. (2021). Herbal Medicine: Clinical Perspective and Regulatory Status. Combinatorial Chemistry & High Throughput Screening, 24(10), 1573–1582. https://doi.org/10.2174/1386207323999201110192942
Belhocine, Y., Rahali, S., Allal, H., Assaba, I. M., Ghoniem, M. G., & Ali, F. A. M. (2021). A dispersion corrected dft investigation of the inclusion complexation of dexamethasone with β-cyclodextrin and molecular docking study of its potential activity against covid-19. Molecules, 26(24). https://doi.org/10.3390/molecules26247622
Benaïssa, A., Bouhadiba, A., Naili, N., Chekkal, F., Khelfaoui, M., Bouras, I., Madjram, M. S., Zouchoune, B., Mogalli, S., Malfi, N., Nouar, L., & Madi, F. (2023). Computational investigation of dimethoate and β-cyclodextrin inclusion complex: molecular structures, intermolecular interactions, and electronic analysis. Structural Chemistry, 34(3), 1189–1204. https://doi.org/10.1007/s11224-023-02162-8
Binesh, A., Devaraj, S. N., & Devaraj, H. (2020). Expression of chemokines in macrophage polarization and downregulation of NFκB in aorta allow macrophage polarization by diosgenin in atherosclerosis. Journal of Biochemical and Molecular Toxicology, 34(2). https://doi.org/10.1002/jbt.22422
Binesh, A., Devaraj, S. N., & Halagowder, D. (2018). Atherogenic diet induced lipid accumulation induced NFκB level in heart, liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent. Life Sciences, 196, 28–37. https://doi.org/10.1016/j.lfs.2018.01.012
Braga, S. S., Lysenko, K., El-Saleh, F., & Paz, F. A. A. (2021). Cyclodextrin-Efavirenz Complexes Investigated by Solid State and Solubility Studies. 15. https://doi.org/10.3390/iecp2020-08690
Cid-Samamed, A., Rakmai, J., Mejuto, J. C., Simal-Gandara, J., & Astray, G. (2022). Cyclodextrins inclusion complex: Preparation methods, analytical techniques and food industry applications. In Food Chemistry (Vol. 384). Elsevier Ltd. https://doi.org/10.1016/j.foodchem.2022.132467
Crini, G. (2014). Review: A history of cyclodextrins. In Chemical Reviews (Vol. 114, Issue 21, pp. 10940–10975). American Chemical Society. https://doi.org/10.1021/cr500081p
Crini, G., Fourmentin, S., Fenyvesi, É., Torri, G., Fourmentin, M., & Morin-Crini, N. (2018). Cyclodextrins, from molecules to applications. In Environmental Chemistry Letters (Vol. 16, Issue 4, pp. 1361–1375). Springer Verlag. https://doi.org/10.1007/s10311-018-0763-2
da Silva Júnior, W. F., de Oliveira Pinheiro, J. G., Moreira, C. D. L. F. A., de Souza, F. J. J., & de Lima, Á. A. N. (2017). Alternative Technologies to Improve Solubility and Stability of Poorly Water-Soluble Drugs. In Multifunctional Systems for Combined Delivery, Biosensing and Diagnostics (pp. 281–305). Elsevier. https://doi.org/10.1016/B978-0-323-52725-5.00015-0
Gan, Q., Wang, J., Hu, J., Lou, G., Xiong, H., Peng, C., Zheng, S., & Huang, Q. (2020). The role of diosgenin in diabetes and diabetic complications. In Journal of Steroid Biochemistry and Molecular Biology (Vol. 198). Elsevier Ltd. https://doi.org/10.1016/j.jsbmb.2019.105575
Han, P., Zhong, Y., An, N., Lu, S., Wang, Q., & Dong, J. (2021). Preparation, characterization, and molecular modeling of sesamol/β-cyclodextrin derivatives inclusion complexes. Journal of Molecular Liquids, 339. https://doi.org/10.1016/j.molliq.2021.116790
Hotarat, W., Phunpee, S., Rungnim, C., Wolschann, P., Kungwan, N., Ruktanonchai, U., Rungrotmongkol, T., & Hannongbua, S. (2019). Encapsulation of alpha-mangostin and hydrophilic beta-cyclodextrins revealed by all-atom molecular dynamics simulations. Journal of Molecular Liquids, 288. https://doi.org/10.1016/j.molliq.2019.110965
Jadhav, P., Petkar, B., Pore, Y., Kulkarni, A., & Burade, K. (2013). Physicochemical and molecular modeling studies of cefixime-l-arginine- cyclodextrin ternary inclusion compounds. Carbohydrate Polymers, 98(2), 1317–1325. https://doi.org/10.1016/j.carbpol.2013.07.070
Kaur, K., Jindal, R., & Jindal, D. (2019). Synthesis, characterization and studies on host-guest interactions of inclusion complexes of metformin hydrochloride with β–cyclodextrin. Journal of Molecular Liquids, 282, 162–168. https://doi.org/10.1016/j.molliq.2019.02.127
Leach, A. R., Research, G. W., Harlow, P., London, E. •, New, •, Boston, Y. •, Francisco, S., Toronto, •, Singapore, S. •, Horg, •, Tokyo, K., Seoul, •, Taipei, •, Cape, D. •, Madrid, T. •, Mexico, •, Amsterdam, G. •, & Munich -Pans, •. (n.d.). Molecular Modelling PRINCIPLES AND APPLICATIONS Second edition.
Luo, Z., Hu, Y., Wang, L., Yin, X., Ma, X., Yang, H., & Zhao, Z. (2018). Study on the Synthesis and Bioactivity of Diosgenin Antitumor Derivatives. Chinese Journal of Organic Chemistry, 38(4), 919–925. https://doi.org/10.6023/cjoc201711016
Monitoring health for the SDGs, Sustainable Development Goals. (n.d.).
Mora, S., & Manson, J. A. E. (2016). Aspirin for primary prevention of atherosclerotic cardiovascular disease: Advances in diagnosis and treatment. In JAMA Internal Medicine (Vol. 176, Issue 8, pp. 1195–1204). American Medical Association. https://doi.org/10.1001/jamainternmed.2016.2648
Mumit, M. A., Pal, T. K., Alam, M. A., Islam, M. A. A. A. A., Paul, S., & Sheikh, M. C. (2020). DFT studies on vibrational and electronic spectra, HOMO–LUMO, MEP, HOMA, NBO and molecular docking analysis of benzyl-3-N-(2,4,5-trimethoxyphenylmethylene)hydrazinecarbodithioate. Journal of Molecular Structure, 1220. https://doi.org/10.1016/j.molstruc.2020.128715
Muttaqin, F. Z., Restisari, I. H., & Muhammad, H. N. (2021). Study of Molecular Docking, Molecular Dynamic and Toxicity Prediction of Several Quinoline Alkaloid Derivatives as a Bruton Tyrosine Kinase Inhibitor as Anti-Leukemia. Journal of Drug Delivery and Therapeutics, 11(6-S), 70–78. https://doi.org/10.22270/jddt.v11i6-s.5135
Papaioannou, A., Christoforides, E., & Bethanis, K. (2020). Inclusion complexes of naringenin in dimethylated and permethylated β-cyclodextrins: Crystal structures and molecular dynamics studies. Crystals, 10(1). https://doi.org/10.3390/cryst10010010
Philip F. Builders. (2019). Herbal Medicine. IntechOpen.
Rismawanti, R., & Saidah, S. (n.d.). REVIEW: ACTIVITY OF DIOSGENIN COMPOUND AS ATHEROSCLEROSIS THERAPY. In Medical Sains : Jurnal Ilmiah Kefarmasian (Vol. 9, Issue 2). https://www.creativecommons.org/licenses/by-sa/4.0/
Sliwoski, G., Kothiwale, S., Meiler, J., & Lowe, E. W. (2014). Computational methods in drug discovery. In Pharmacological Reviews (Vol. 66, Issue 1, pp. 334–395). https://doi.org/10.1124/pr.112.007336
Sogut, O., Aydemir Sezer, U., & Sezer, S. (2021). Liposomal delivery systems for herbal extracts. In Journal of Drug Delivery Science and Technology (Vol. 61). Editions de Sante. https://doi.org/10.1016/j.jddst.2020.102147
Valdés-Tresanco, M. S., Valdés-Tresanco, M. E., Valiente, P. A., & Moreno, E. (2020). AMDock: a versatile graphical tool for assisting molecular docking with Autodock Vina and Autodock4. Biology Direct, 15(1). https://doi.org/10.1186/s13062-020-00267-2
Wang, C., Niimi, M., Watanabe, T., Wang, Y., Liang, J., & Fan, J. (2018). Treatment of atherosclerosis by traditional Chinese medicine: Questions and quandaries. In Atherosclerosis (Vol. 277, pp. 136–144). Elsevier Ireland Ltd. https://doi.org/10.1016/j.atherosclerosis.2018.08.039
Wang, H., Zhu, H., & Yang, X. (2020). Dioscin exhibits anti-inflammatory effects in IL-1β-stimulated human osteoarthritis chondrocytes by activating LXRα. Immunopharmacology and Immunotoxicology, 42(4), 340–345. https://doi.org/10.1080/08923973.2020.1775248
World Health Organization. (2024). Monitoring health for the SDGs, Sustainable Development Goals.
Zhong, Y., Li, W., Ran, L., Hou, R., Han, P., Lu, S., Wang, Q., Zhao, W., Zhu, Y., & Dong, J. (2020). Inclusion complexes of tea polyphenols with HP-β-cyclodextrin:Preparation, characterization, molecular docking, and antioxidant activity. Journal of Food Science, 85(4), 1105–1113. https://doi.org/10.1111/1750-3841.15083
Asnawi, A., Febrina, E., Aligita, W., Yuliantini, A., & Arfan, A. (2023). Penambatan Molekul dan Dinamika Molekul beberapa Fitokimia dari Acalypha Indica L. sebagai Inhibitor Matriks Metalloproteinase9. Jurnal Sains Farmasi & Klinis, 10(1), 62. https://doi.org/10.25077/jsfk.10.1.62-70.2023
Aumsuwan, P., Khan, S. I., Khan, I. A., Ali, Z., Avula, B., Walker, L. A., Shariat-Madar, Z., Helferich, W. G., Katzenellenbogen, B. S., & Dasmahapatra, A. K. (2016). The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro. Archives of Biochemistry and Biophysics, 591, 98–110. https://doi.org/10.1016/j.abb.2015.12.001
Barkat, Md. A., Goyal, A., Barkat, H. A., Salauddin, M., Pottoo, F. H., & Anwer, E. T. (2021). Herbal Medicine: Clinical Perspective and Regulatory Status. Combinatorial Chemistry & High Throughput Screening, 24(10), 1573–1582. https://doi.org/10.2174/1386207323999201110192942
Belhocine, Y., Rahali, S., Allal, H., Assaba, I. M., Ghoniem, M. G., & Ali, F. A. M. (2021). A dispersion corrected dft investigation of the inclusion complexation of dexamethasone with β-cyclodextrin and molecular docking study of its potential activity against covid-19. Molecules, 26(24). https://doi.org/10.3390/molecules26247622
Benaïssa, A., Bouhadiba, A., Naili, N., Chekkal, F., Khelfaoui, M., Bouras, I., Madjram, M. S., Zouchoune, B., Mogalli, S., Malfi, N., Nouar, L., & Madi, F. (2023). Computational investigation of dimethoate and β-cyclodextrin inclusion complex: molecular structures, intermolecular interactions, and electronic analysis. Structural Chemistry, 34(3), 1189–1204. https://doi.org/10.1007/s11224-023-02162-8
Binesh, A., Devaraj, S. N., & Devaraj, H. (2020). Expression of chemokines in macrophage polarization and downregulation of NFκB in aorta allow macrophage polarization by diosgenin in atherosclerosis. Journal of Biochemical and Molecular Toxicology, 34(2). https://doi.org/10.1002/jbt.22422
Binesh, A., Devaraj, S. N., & Halagowder, D. (2018). Atherogenic diet induced lipid accumulation induced NFκB level in heart, liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent. Life Sciences, 196, 28–37. https://doi.org/10.1016/j.lfs.2018.01.012
Braga, S. S., Lysenko, K., El-Saleh, F., & Paz, F. A. A. (2021). Cyclodextrin-Efavirenz Complexes Investigated by Solid State and Solubility Studies. 15. https://doi.org/10.3390/iecp2020-08690
Cid-Samamed, A., Rakmai, J., Mejuto, J. C., Simal-Gandara, J., & Astray, G. (2022). Cyclodextrins inclusion complex: Preparation methods, analytical techniques and food industry applications. In Food Chemistry (Vol. 384). Elsevier Ltd. https://doi.org/10.1016/j.foodchem.2022.132467
Crini, G. (2014). Review: A history of cyclodextrins. In Chemical Reviews (Vol. 114, Issue 21, pp. 10940–10975). American Chemical Society. https://doi.org/10.1021/cr500081p
Crini, G., Fourmentin, S., Fenyvesi, É., Torri, G., Fourmentin, M., & Morin-Crini, N. (2018). Cyclodextrins, from molecules to applications. In Environmental Chemistry Letters (Vol. 16, Issue 4, pp. 1361–1375). Springer Verlag. https://doi.org/10.1007/s10311-018-0763-2
da Silva Júnior, W. F., de Oliveira Pinheiro, J. G., Moreira, C. D. L. F. A., de Souza, F. J. J., & de Lima, Á. A. N. (2017). Alternative Technologies to Improve Solubility and Stability of Poorly Water-Soluble Drugs. In Multifunctional Systems for Combined Delivery, Biosensing and Diagnostics (pp. 281–305). Elsevier. https://doi.org/10.1016/B978-0-323-52725-5.00015-0
Gan, Q., Wang, J., Hu, J., Lou, G., Xiong, H., Peng, C., Zheng, S., & Huang, Q. (2020). The role of diosgenin in diabetes and diabetic complications. In Journal of Steroid Biochemistry and Molecular Biology (Vol. 198). Elsevier Ltd. https://doi.org/10.1016/j.jsbmb.2019.105575
Han, P., Zhong, Y., An, N., Lu, S., Wang, Q., & Dong, J. (2021). Preparation, characterization, and molecular modeling of sesamol/β-cyclodextrin derivatives inclusion complexes. Journal of Molecular Liquids, 339. https://doi.org/10.1016/j.molliq.2021.116790
Hotarat, W., Phunpee, S., Rungnim, C., Wolschann, P., Kungwan, N., Ruktanonchai, U., Rungrotmongkol, T., & Hannongbua, S. (2019). Encapsulation of alpha-mangostin and hydrophilic beta-cyclodextrins revealed by all-atom molecular dynamics simulations. Journal of Molecular Liquids, 288. https://doi.org/10.1016/j.molliq.2019.110965
Jadhav, P., Petkar, B., Pore, Y., Kulkarni, A., & Burade, K. (2013). Physicochemical and molecular modeling studies of cefixime-l-arginine- cyclodextrin ternary inclusion compounds. Carbohydrate Polymers, 98(2), 1317–1325. https://doi.org/10.1016/j.carbpol.2013.07.070
Kaur, K., Jindal, R., & Jindal, D. (2019). Synthesis, characterization and studies on host-guest interactions of inclusion complexes of metformin hydrochloride with β–cyclodextrin. Journal of Molecular Liquids, 282, 162–168. https://doi.org/10.1016/j.molliq.2019.02.127
Leach, A. R., Research, G. W., Harlow, P., London, E. •, New, •, Boston, Y. •, Francisco, S., Toronto, •, Singapore, S. •, Horg, •, Tokyo, K., Seoul, •, Taipei, •, Cape, D. •, Madrid, T. •, Mexico, •, Amsterdam, G. •, & Munich -Pans, •. (n.d.). Molecular Modelling PRINCIPLES AND APPLICATIONS Second edition.
Luo, Z., Hu, Y., Wang, L., Yin, X., Ma, X., Yang, H., & Zhao, Z. (2018). Study on the Synthesis and Bioactivity of Diosgenin Antitumor Derivatives. Chinese Journal of Organic Chemistry, 38(4), 919–925. https://doi.org/10.6023/cjoc201711016
Monitoring health for the SDGs, Sustainable Development Goals. (n.d.).
Mora, S., & Manson, J. A. E. (2016). Aspirin for primary prevention of atherosclerotic cardiovascular disease: Advances in diagnosis and treatment. In JAMA Internal Medicine (Vol. 176, Issue 8, pp. 1195–1204). American Medical Association. https://doi.org/10.1001/jamainternmed.2016.2648
Mumit, M. A., Pal, T. K., Alam, M. A., Islam, M. A. A. A. A., Paul, S., & Sheikh, M. C. (2020). DFT studies on vibrational and electronic spectra, HOMO–LUMO, MEP, HOMA, NBO and molecular docking analysis of benzyl-3-N-(2,4,5-trimethoxyphenylmethylene)hydrazinecarbodithioate. Journal of Molecular Structure, 1220. https://doi.org/10.1016/j.molstruc.2020.128715
Muttaqin, F. Z., Restisari, I. H., & Muhammad, H. N. (2021). Study of Molecular Docking, Molecular Dynamic and Toxicity Prediction of Several Quinoline Alkaloid Derivatives as a Bruton Tyrosine Kinase Inhibitor as Anti-Leukemia. Journal of Drug Delivery and Therapeutics, 11(6-S), 70–78. https://doi.org/10.22270/jddt.v11i6-s.5135
Papaioannou, A., Christoforides, E., & Bethanis, K. (2020). Inclusion complexes of naringenin in dimethylated and permethylated β-cyclodextrins: Crystal structures and molecular dynamics studies. Crystals, 10(1). https://doi.org/10.3390/cryst10010010
Philip F. Builders. (2019). Herbal Medicine. IntechOpen.
Rismawanti, R., & Saidah, S. (n.d.). REVIEW: ACTIVITY OF DIOSGENIN COMPOUND AS ATHEROSCLEROSIS THERAPY. In Medical Sains : Jurnal Ilmiah Kefarmasian (Vol. 9, Issue 2). https://www.creativecommons.org/licenses/by-sa/4.0/
Sliwoski, G., Kothiwale, S., Meiler, J., & Lowe, E. W. (2014). Computational methods in drug discovery. In Pharmacological Reviews (Vol. 66, Issue 1, pp. 334–395). https://doi.org/10.1124/pr.112.007336
Sogut, O., Aydemir Sezer, U., & Sezer, S. (2021). Liposomal delivery systems for herbal extracts. In Journal of Drug Delivery Science and Technology (Vol. 61). Editions de Sante. https://doi.org/10.1016/j.jddst.2020.102147
Valdés-Tresanco, M. S., Valdés-Tresanco, M. E., Valiente, P. A., & Moreno, E. (2020). AMDock: a versatile graphical tool for assisting molecular docking with Autodock Vina and Autodock4. Biology Direct, 15(1). https://doi.org/10.1186/s13062-020-00267-2
Wang, C., Niimi, M., Watanabe, T., Wang, Y., Liang, J., & Fan, J. (2018). Treatment of atherosclerosis by traditional Chinese medicine: Questions and quandaries. In Atherosclerosis (Vol. 277, pp. 136–144). Elsevier Ireland Ltd. https://doi.org/10.1016/j.atherosclerosis.2018.08.039
Wang, H., Zhu, H., & Yang, X. (2020). Dioscin exhibits anti-inflammatory effects in IL-1β-stimulated human osteoarthritis chondrocytes by activating LXRα. Immunopharmacology and Immunotoxicology, 42(4), 340–345. https://doi.org/10.1080/08923973.2020.1775248
World Health Organization. (2024). Monitoring health for the SDGs, Sustainable Development Goals.
Zhong, Y., Li, W., Ran, L., Hou, R., Han, P., Lu, S., Wang, Q., Zhao, W., Zhu, Y., & Dong, J. (2020). Inclusion complexes of tea polyphenols with HP-β-cyclodextrin:Preparation, characterization, molecular docking, and antioxidant activity. Journal of Food Science, 85(4), 1105–1113. https://doi.org/10.1111/1750-3841.15083