Screening of Chrysin and its Derivatives for their Binding Affinity to Human Histone Deacetylases (Hdacs): A Computer-Aided Approach

Igwe K K, Otuokere I, Ikpeazu O V, Amaku J F

Abstract


Repositioning chrysin and chrysin-analogue as possible human histone deacetylases (PDB ID: 1t64) inhibitor was investigated. The chrysin-analogue CHD1, Chrysin, CHD2, CHD3, CHD4, CHD5, CHD6, CHD7,CHD8, CHD9 and CHD10 was noticed to have docking score of -7.8 kcal/mol, -7.6 kcal/mol, -7.6 kcal/mol, -7.3 kcal/mol, -7.2 kcal/mol, -7.2 kcal/mol, -7.1 kcal/mol, -6.9 kcal/mol, -6.9 kcal/mol,, -6.4 kcal/mol, and -5.7 kcal/mol respectively.  The lead molecule (4-(5,7-dihydroxy-4-oxo-4H-1-benzopyran-2-yl)-2,6-dimethoxybenzene-1-sulfonyl chloride) was noticed to interact with MET 261, PRO 260, TYR 87, GLY 292, TYR 293, LEU 295, ARG 24, PRO 22, ILE 21, LEU 18, TYR 98, TRP 128, TYR 141 and PHE 139.  The lead molecule demonstrated good pharmacokinetics and drug-like characteristic.  Hence, 4-(5,7-dihydroxy-4-oxo-4H-1-benzopyran-2-yl)-2,6-dimethoxybenzene-1-sulfonyl chloride is a promising compound that should be further examined as drug candidates


Keywords


Chrysin, Molecular Docking, ADMET, Bioactive Compound, Pharmacophore

Full Text:

PDF

References


Robards, K. and M. Antolovich, Analytical chemistry of fruit bioflavonoidsA review. Analyst, 1997. 122(2): p. 11R-34R.

Pietta, P.-G., Flavonoids as antioxidants. Journal of natural products, 2000. 63(7): p. 1035-1042.

Nijveldt, R.J., et al., Flavonoids: a review of probable mechanisms of action and potential applications. The American journal of clinical nutrition, 2001. 74(4): p. 418-425.

Kale, A., S. Gawande, and S. Kotwal, Cancer phytotherapeutics: role for flavonoids at the cellular level. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 2008. 22(5): p. 567-577.

Awad, R., et al., Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties. Phytomedicine, 2003. 10(8): p. 640-649.

Zheng, X., et al., Synthesis and anticancer effect of chrysin derivatives. Bioorganic & Medicinal Chemistry Letters, 2003. 13(5): p. 881-884.

Ernst, E., Herbal remedies for anxiety–a systematic review of controlled clinical trials. Phytomedicine, 2006. 13(3): p. 205-208.

Huang, W.-H., A.-R. Lee, and C.-H. Yang, Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI. Bioscience, biotechnology, and biochemistry, 2006. 70(10): p. 2371-2380.

Scheck, A.C., et al., Anticancer activity of extracts derived from the mature roots of Scutellaria baicalensis on human malignant brain tumor cells. BMC Complementary and Alternative Medicine, 2006. 6(1): p. 27.

Cole, I.B., et al., Comparisons of Scutellaria baicalensis, Scutellaria lateriflora and Scutellaria racemosa: genome size, antioxidant potential and phytochemistry. Planta medica, 2008. 74(4): p. 474.

Parajuli, P., et al., In vitro antitumor mechanisms of various Scutellaria extracts and constituent flavonoids. 2009.

Chan, E.C., P. Pannangpetch, and O.L. Woodman, Relaxation to flavones and flavonols in rat isolated thoracic aorta: mechanism of action and structure-activity relationships. Journal of cardiovascular pharmacology, 2000. 35(2): p. 326-333.

Woodman, O.L. and E.C. Chan, Vascular and anti‐oxidant actions of flavonols and flavones. Clinical and Experimental Pharmacology and Physiology, 2004. 31(11): p. 786-790.

Lee, J., et al., Use of flavones, coumarins and related compounds to treat infections. Saengyak Hakhoe Chi, 1999. 30: p. 34-9.

Babu, K.S., et al., Synthesis and biological evaluation of novel C (7) modified chrysin analogues as antibacterial agents. Bioorganic & medicinal chemistry letters, 2006. 16(1): p. 221-224.

Cho, H., et al., Modulation of the activity of pro-inflammatory enzymes, COX-2 and iNOS, by chrysin derivatives. Pharmacological Research, 2004. 49(1): p. 37-43.

Zanoli, P., R. Avallone, and M. Baraldi, Behavioral characterisation of the flavonoids apigenin and chrysin. Fitoterapia, 2000. 71: p. S117-S123.

Sanderson, J.T., et al., Induction and inhibition of aromatase (CYP19) activity by natural and synthetic flavonoid compounds in H295R human adrenocortical carcinoma cells. Toxicological Sciences, 2004. 82(1): p. 70-79.

CRITCHFIELD, J.W., S.T. BUTERA, and T.M. FOLKS, Inhibition of HIV activation in latently infected cells by flavonoid compounds. AIDS research and human retroviruses, 1996. 12(1): p. 39-46.

Kubo, I., et al., Flavonols from Heterotheca inuloides: tyrosinase inhibitory activity and structural criteria. Bioorganic & medicinal chemistry, 2000. 8(7): p. 1749-1755.

Khochbin, S., et al., Functional significance of histone deacetylase diversity. Current opinion in genetics & development, 2001. 11(2): p. 162-166.

Johnstone, R.W., Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nature reviews Drug discovery, 2002. 1(4): p. 287-299.

Struhl, K., Histone acetylation and transcriptional regulatory mechanisms. Genes & development, 1998. 12(5): p. 599-606.

Glaser, K.B., et al., Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines. Molecular cancer therapeutics, 2003. 2(2): p. 151-163.

Van Lint, C., S. Emiliani, and E. Verdin, The expression of a small fraction of cellular genes is changed in response to histone hyperacetylation. Gene Expression, The Journal of Liver Research, 1996. 5(4-5): p. 245-253.

Hanwell, M.D., et al., Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. Journal of cheminformatics, 2012. 4(1): p. 17.

Pettersen, E.F., et al., UCSF Chimera—a visualization system for exploratory research and analysis. Journal of computational chemistry, 2004. 25(13): p. 1605-1612.

Morris, G.M., et al., Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of computational chemistry, 1998. 19(14): p. 1639-1662.




DOI: http://dx.doi.org/10.52155/ijpsat.v22.1.2019

Refbacks

  • There are currently no refbacks.


Copyright (c) 2020 Igwe K K, Otuokere I, Ikpeazu O V, Amaku J F

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.