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Investigation of the interaction between FTO and 3-substituted 2-aminochromones by spectroscopy and molecular modeling

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Abstract

The fat mass and obesity-associated protein is a potential target for anti-obesity medicines. In the present work, the interaction between our synthesized 3-substituted 2-aminochromones and fat mass and obesity-associated protein were investigated using fluorescence spectroscopy, ultraviolet–visible spectroscopy and molecular modeling approach. Fluorescence spectroscopy showed that the fluorescence of fat mass and obesity-associated protein can be quenched by these compounds with a static quenching procedure. In addition, the thermodynamic parameters obtained from the fluorescence data showed that the hydrophobic force played a major role in stabilizing the complexes. Ultraviolet–visible spectroscopy, synchronous fluorescence spectroscopy and three-dimensional fluorescence spectroscopy indicated that these compounds can induce some conformational changes of fat mass and obesity-associated protein.

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References

  • Abbott BM, Thompson PE (2004) PDE2 inhibition by the PI3 kinase inhibitor LY294002 and analogues. Bioorg Med Chem Lett 14:2847–2851

    Article  CAS  PubMed  Google Scholar 

  • Becke AD (1993) Density‐functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652

    Article  CAS  Google Scholar 

  • Berulava T, Ziehe M, Klein-Hitpass L, Mladenov E, Thomale J, Rüther U, Horsthemke B (2013) FTO levels affect RNA modification and the transcriptome. Eur J Hum Genet 21:317–323

    Article  CAS  PubMed  Google Scholar 

  • Chen B, Ye F, Yu L, Jia G, Huang X, Zhang X, Zhang R (2012) Development of cell-active N 6-methyladenosine RNA demethylase FTO inhibitor. J Am Chem Soc 134:17963–17971

    Article  CAS  PubMed  Google Scholar 

  • Chen R, Jiang H, Pu H (2013) Interaction of artemisinin and its derivatives with human serum albumin studied using spectroscopies and molecular modeling methods. Mol Biol Rep 40:4791–4804

    Article  CAS  PubMed  Google Scholar 

  • Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Cox RD (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 42:1086–1092

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De S, Girigoswami A, Das S (2005) Fluorescence probing of albumin–surfactant interaction. J Colloid Interface Sci 285:562–573

    Article  CAS  PubMed  Google Scholar 

  • Di Braccio M, Grossi G, Roma G, Marzano C, Baccichetti F, Simonato M, Bordin F (2003) Pyran derivatives: part XXI. Antiproliferative and cytotoxic properties of novel N-substituted 4-aminocoumarins, their benzo-fused derivatives, and some related 2-aminochromones. Farmaco 58:1083–1097

    Article  PubMed  Google Scholar 

  • Feroz SR, Mohamad SB, Bujang N, Malek SN, Tayyab S (2012) Multispectroscopic and molecular modeling approach to investigate the interaction of flavokawain B with human serum albumin. J Agric Food Chem 60:5899–5908

    Article  CAS  PubMed  Google Scholar 

  • Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Rüther U (2009) Inactivation of the Fto gene protects from obesity. Nature 458:894–898

    Article  CAS  PubMed  Google Scholar 

  • Ge B, Li Z, Yang L, Wang R, Chang J (2015) Characterization of the interaction of FTO protein with thioglycolic acid capped CdTe quantum dots and its analytical application. Spectrochim Acta A 149:667–673

    Article  CAS  Google Scholar 

  • Griffin RJ, Fontana G, Golding BT, Guiard S, Hardcastle IR, Leahy JJ, Smith GC (2005) Selective benzopyranone and pyrimido [2, 1-a] isoquinolin-4-one inhibitors of DNA-dependent protein kinase: synthesis, structure-activity studies, and radiosensitization of a human tumor cell line in vitro. J Med Chem 48:569–585

    Article  CAS  PubMed  Google Scholar 

  • He W, Dou H, Li Z, Wang X, Wang L, Wang R, Chang J (2014) Investigation of the interaction between five alkaloids and human hemoglobin by fluorescence spectroscopy and molecular modeling. Spectrochim Acta A 123:176–186

    Article  CAS  Google Scholar 

  • He W, Li Z, Yang L, Jiang Q, Ren T, Zhang L, Wang R, Chang J (2015) Influence of the ring size on the binding ability of FTO investigated by fluorescence spectroscopy. J Fluoresc 25:1655–1661

    Article  CAS  PubMed  Google Scholar 

  • Hu YJ, Liu Y, Wang JB, Xiao XH, Qu SS (2004) Study of the interaction between monoammonium glycyrrhizinate and bovine serum albumin. J Pharm Biomed 36:915–919

    Article  CAS  Google Scholar 

  • Ibrahim N, Ibrahim H, Kim S, Nallet JP, Nepveu F (2010) Interactions between antimalarial indolone-N-oxide derivatives and human serum albumin. Biomacromolecules 11:3341–3351

    Article  CAS  PubMed  Google Scholar 

  • Kaiser J (2007) Mysterious, widespread obesity gene found through diabetes study. Science 316:185–185

    Article  CAS  PubMed  Google Scholar 

  • Lakowicz JR, Weber G (1973) Quenching of fluorescence by oxygen. Probe for structural fluctuations in macromolecules. Biochemistry 12:4161–4170

    Article  CAS  PubMed  Google Scholar 

  • Leahy JJ, Golding BT, Griffin RJ, Hardcastle IR, Richardson C, Rigoreau L, Smith GC (2004) Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg Med Chem Lett 14:6083–6087

    Article  CAS  PubMed  Google Scholar 

  • Lehrer S (1971) Solute perturbation of protein fluorescence. Quenching of the tryptophyl fluorescence of model compounds and of lysozyme by iodide ion. Biochemistry 10:3254–3263

    Article  CAS  PubMed  Google Scholar 

  • Lissi E, Abuin E, Lanio ME, Alvarez C (2002) A new and simple procedure for the evaluation of the association of surfactants to proteins. J Biochem Biophys Methods 50:261–268

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Yang Y, Wang S, Wu J, Wang XN, Chang J (2015) Synthesis of 3-substituted 2-aminochromones via Sn (IV)-promoted annulation of Ynamides with 2-methoxyaroyl chlorides. Org Lett 17:4472–4475

    Article  CAS  PubMed  Google Scholar 

  • Liu J, Yue Y, Wang J, Yan X, Liu R, Sun Y, Li X (2015) Study of interaction between human serum albumin and three phenanthridine derivatives: fluorescence spectroscopy and computational approach. Spectrochim Acta A 145:473–481

    Article  CAS  Google Scholar 

  • Li Z, Li Z, Yang L, Xie Y, Shi J, Wang R, Chang J (2015) Investigation of the binding between pepsin and nucleoside analogs by spectroscopy and molecular simulation. J Fluoresc 25:451–463

    Article  CAS  PubMed  Google Scholar 

  • MacManus-Spencer LA, Tse ML, Hebert PC, Bischel HN, Luthy RG (2009) Binding of perfluorocarboxylates to serum albumin: a comparison of analytical methods. Anal Chem 82:974–981

    Article  Google Scholar 

  • Messina PV, Prieto G, Ruso JM, Sarmiento F (2005) Conformational changes in human serum albumin induced by sodium perfluorooctanoate in aqueous solutions. J Phys Chem B 109:15566–15573

    Article  CAS  PubMed  Google Scholar 

  • Morris J, Wishka DG, Lin AH, Humphrey WR, Wiltse AL, Gammill RB, Olds NL (1993) Synthesis and biological evaluation of antiplatelet 2-aminochromones. J Med Chem 36:2026–2032

    Article  CAS  PubMed  Google Scholar 

  • Patil S, Sandberg A, Heckert E, Self W, Seal S (2007) Protein adsorption and cellular uptake of cerium oxide nanoparticles as a function of zeta potential. Biomaterials 28:4600–4607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin C, Xie MX, Liu Y (2007) Characterization of the myricetin-human serum albumin complex by spectroscopic and molecular modeling approaches. Biomacromolecules 8:2182–2189

    Article  CAS  PubMed  Google Scholar 

  • Rakotoarivelo NV, Perio P, Najahi E, Nepveu F (2014) Interaction between antimalarial 2-aryl-3 h-indol-3-one derivatives and human serum albumin. J Phys Chem B 118:13477–13485

    Article  CAS  PubMed  Google Scholar 

  • Roma G, Cinone N, Di Braccio M, Grossi G, Leoncini G, Signorello MG, Carotti A (2000) Synthesis, antiplatelet activity and comparative molecular field analysis of substituted 2-amino-4H-pyrido [1, 2-a] pyrimidin-4-ones, their congeners and isosteric analogues. Bioorg Med Chem 8:751–768

    Article  CAS  PubMed  Google Scholar 

  • Roma G, Di Braccio M, Grossi G, Marzano C, Simonato M, Bordin F (1998) Pyran derivatives XX. 2-aminochromone benzo-fused derivatives with antiproliferative properties. Farmaco 53:494–503

    Article  CAS  PubMed  Google Scholar 

  • Ross PD, Subramanian S (1981) Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20:3096–3102

    Article  CAS  PubMed  Google Scholar 

  • Sabín J, Prieto G, González-Pérez A, Ruso JM, Sarmiento F (2006) Effects of fluorinated and hydrogenated surfactants on human serum albumin at different pHs. Biomacromolecules 7:176–182

    Article  PubMed  Google Scholar 

  • Shu Y, Xue W, Xu X, Jia Z, Yao X, Liu S, Liu L (2015) Interaction of erucic acid with bovine serum albumin using a multi-spectroscopic method and molecular docking technique. Food Chem 173:31–37

    Article  CAS  PubMed  Google Scholar 

  • Śliwińska-Hill U (2017) Interaction of imatinib mesylate with human serum transferrin: the comparative spectroscopic studies. Spectrochim Acta A 173:468–475

    Article  Google Scholar 

  • Tayyab S, Izzudin MM, Kabir MZ, Feroz SR, Tee WV, Mohamad SB, Alias Z (2016) Binding of an anticancer drug, axitinib to human serum albumin: Fluorescence quenching and molecular docking study. J Photochem Photobiol B 162:386–394

    Article  CAS  PubMed  Google Scholar 

  • Tung YCL, Ayuso E, Shan X, Bosch F, O’Rahilly S, Coll AP, Yeo GS (2010) Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats. PloS One 5:e8771

    Article  PubMed  PubMed Central  Google Scholar 

  • Vlahos CJ, Matter WF, Hui KY, Brown RF (1994) A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem 269:5241–5248

    CAS  PubMed  Google Scholar 

  • Wang P, Yang FJ, Du H, Guan YF, Xu TY, Xu XW, Miao CY (2011) Involvement of leptin receptor (LepRb)-STAT3 signaling pathway in brain FTO downregulation during energy restriction. Mol Med 17:523–532

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang R, Dou H, Yin Y, Xie Y, Sun L, Liu C, Chang J (2014) Investigation of the interaction between isomeric derivatives and human serum albumin by fluorescence spectroscopy and molecular modeling. J Lumin 154:8–14

    Article  CAS  Google Scholar 

  • Wang R, Xie Y, Zhang Y, Kang X, Wang X, Ge B, Chang J (2013) Comparative study of the binding of pepsin to four alkaloids by spectrofluorimetry. Spectrochim Acta A 108:62–74

    Article  Google Scholar 

  • Ware WR (1962) Oxygen quenching of fluorescence in solution: an experimental study of the diffusion process. J Phys Chem 66:455–458

    Article  CAS  Google Scholar 

  • Wei J, Jin F, Wu Q, Jiang Y, Gao D, Liu H (2014) Molecular interaction study of flavonoid derivative 3d with human serum albumin using multispectroscopic and molecular modeling approach. Talanta 126:116–121

    Article  CAS  PubMed  Google Scholar 

  • Yan CN, Zhang HX, Mei P, Liu Y (2005) Study on binding reaction between flucytosine and bovine serum albumin. Chin J Chem 23:1151–1156

    Article  CAS  Google Scholar 

  • Zhang H, Huang X, Zhang M (2008) Spectral diagnostics of the interaction between pyridoxine hydrochloride and bovine serum albumin in vitro. Mol Biol Rep 35:699–705

    Article  CAS  PubMed  Google Scholar 

  • Zhang P, Liu D, Li Z, Shen Z, Wang P, Zhou M, Zhu W (2014) Multispectroscopic and molecular modeling approach to investigate the interaction of diclofop-methyl enantiomers with human serum albumin. J Lumin 155:231–237

    Article  CAS  Google Scholar 

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Acknowledgements

We are grateful to the National Natural Science Foundation of China (No. 81330075), and 2015 Key science and technology plan project of Henan province (152102310065) for financial support.

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Correspondence to Ruiyong Wang or Junbiao Chang.

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Zhang, L., Wang, Z., Ren, T. et al. Investigation of the interaction between FTO and 3-substituted 2-aminochromones by spectroscopy and molecular modeling. Med Chem Res 26, 1349–1358 (2017). https://doi.org/10.1007/s00044-017-1873-2

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  • DOI: https://doi.org/10.1007/s00044-017-1873-2

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