Medicinal Chemistry Research

, Volume 26, Issue 7, pp 1349–1358 | Cite as

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

  • Lijiao Zhang
  • Zechun Wang
  • Ting Ren
  • Hongxu Liu
  • Xiaona Wang
  • Ruiyong Wang
  • Junbiao Chang
Original Research


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.


FTO 3-Substituted 2-aminochromones Fluorescence Interaction Molecular modeling 



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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1873_MOESM1_ESM.pdf (2.1 mb)
Supplementary Information
44_2017_1873_MOESM2_ESM.doc (1 mb)
Supplementary Information


  1. Abbott BM, Thompson PE (2004) PDE2 inhibition by the PI3 kinase inhibitor LY294002 and analogues. Bioorg Med Chem Lett 14:2847–2851CrossRefPubMedGoogle Scholar
  2. Becke AD (1993) Density‐functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652CrossRefGoogle Scholar
  3. 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 21:317–323CrossRefPubMedGoogle Scholar
  4. 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 134:17963–17971CrossRefPubMedGoogle Scholar
  5. 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 40:4791–4804CrossRefPubMedGoogle Scholar
  6. 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 42:1086–1092CrossRefPubMedPubMedCentralGoogle Scholar
  7. De S, Girigoswami A, Das S (2005) Fluorescence probing of albumin–surfactant interaction. J Colloid Interface Sci 285:562–573CrossRefPubMedGoogle Scholar
  8. 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 58:1083–1097CrossRefPubMedGoogle Scholar
  9. 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 60:5899–5908CrossRefPubMedGoogle Scholar
  10. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Rüther U (2009) Inactivation of the Fto gene protects from obesity. Nature 458:894–898CrossRefPubMedGoogle Scholar
  11. 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 149:667–673CrossRefGoogle Scholar
  12. 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 48:569–585CrossRefPubMedGoogle Scholar
  13. 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 123:176–186CrossRefGoogle Scholar
  14. 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 25:1655–1661CrossRefPubMedGoogle Scholar
  15. 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 36:915–919CrossRefGoogle Scholar
  16. Ibrahim N, Ibrahim H, Kim S, Nallet JP, Nepveu F (2010) Interactions between antimalarial indolone-N-oxide derivatives and human serum albumin. Biomacromolecules 11:3341–3351CrossRefPubMedGoogle Scholar
  17. Kaiser J (2007) Mysterious, widespread obesity gene found through diabetes study. Science 316:185–185CrossRefPubMedGoogle Scholar
  18. Lakowicz JR, Weber G (1973) Quenching of fluorescence by oxygen. Probe for structural fluctuations in macromolecules. Biochemistry 12:4161–4170CrossRefPubMedGoogle Scholar
  19. 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 14:6083–6087CrossRefPubMedGoogle Scholar
  20. Lehrer S (1971) Solute perturbation of protein fluorescence. Quenching of the tryptophyl fluorescence of model compounds and of lysozyme by iodide ion. Biochemistry 10:3254–3263CrossRefPubMedGoogle Scholar
  21. 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 50:261–268CrossRefPubMedGoogle Scholar
  22. 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 17:4472–4475CrossRefPubMedGoogle Scholar
  23. 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 145:473–481CrossRefGoogle Scholar
  24. 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 25:451–463CrossRefPubMedGoogle Scholar
  25. 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 82:974–981CrossRefGoogle Scholar
  26. 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 109:15566–15573CrossRefPubMedGoogle Scholar
  27. 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 36:2026–2032CrossRefPubMedGoogle Scholar
  28. 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 28:4600–4607CrossRefPubMedPubMedCentralGoogle Scholar
  29. Qin C, Xie MX, Liu Y (2007) Characterization of the myricetin-human serum albumin complex by spectroscopic and molecular modeling approaches. Biomacromolecules 8:2182–2189CrossRefPubMedGoogle Scholar
  30. 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 118:13477–13485CrossRefPubMedGoogle Scholar
  31. 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 8:751–768CrossRefPubMedGoogle Scholar
  32. 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 53:494–503CrossRefPubMedGoogle Scholar
  33. Ross PD, Subramanian S (1981) Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry 20:3096–3102CrossRefPubMedGoogle Scholar
  34. 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 7:176–182CrossRefPubMedGoogle Scholar
  35. 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 173:31–37CrossRefPubMedGoogle Scholar
  36. Śliwińska-Hill U (2017) Interaction of imatinib mesylate with human serum transferrin: the comparative spectroscopic studies. Spectrochim Acta A 173:468–475CrossRefGoogle Scholar
  37. 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 162:386–394CrossRefPubMedGoogle Scholar
  38. 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:e8771CrossRefPubMedPubMedCentralGoogle Scholar
  39. 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 269:5241–5248PubMedGoogle Scholar
  40. 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 17:523–532PubMedPubMedCentralGoogle Scholar
  41. 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 154:8–14CrossRefGoogle Scholar
  42. 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 108:62–74CrossRefGoogle Scholar
  43. Ware WR (1962) Oxygen quenching of fluorescence in solution: an experimental study of the diffusion process. J Phys Chem 66:455–458CrossRefGoogle Scholar
  44. 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 126:116–121CrossRefPubMedGoogle Scholar
  45. Yan CN, Zhang HX, Mei P, Liu Y (2005) Study on binding reaction between flucytosine and bovine serum albumin. Chin J Chem 23:1151–1156CrossRefGoogle Scholar
  46. Zhang H, Huang X, Zhang M (2008) Spectral diagnostics of the interaction between pyridoxine hydrochloride and bovine serum albumin in vitro. Mol Biol Rep 35:699–705CrossRefPubMedGoogle Scholar
  47. 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 155:231–237CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.College of Chemistry and Molecular EngineeringZhengzhou UniversityZhengzhouChina

Personalised recommendations