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Zhou J, Lu G, Wang H, et al. Molecular structure-affinity relationship of bufadienolides and human serum albumin in vitro and molecular docking analysis. PLoS One. 2015;10(5):e0126669doi: 10.1371/journal.pone.0126669.
Zhou, J., Lu, G., Wang, H., Zhang, J., Duan, J., Ma, H., & Wu, Q. (2015). Molecular structure-affinity relationship of bufadienolides and human serum albumin in vitro and molecular docking analysis. PloS one, 10(5), e0126669. https://doi.org/10.1371/journal.pone.0126669
Zhou, Jing, et al. "Molecular structure-affinity relationship of bufadienolides and human serum albumin in vitro and molecular docking analysis." PloS one vol. 10,5 (2015): e0126669. doi: https://doi.org/10.1371/journal.pone.0126669
Zhou J, Lu G, Wang H, Zhang J, Duan J, Ma H, Wu Q. Molecular structure-affinity relationship of bufadienolides and human serum albumin in vitro and molecular docking analysis. PLoS One. 2015 May 06;10(5):e0126669. doi: 10.1371/journal.pone.0126669. eCollection 2015. PMID: 25946161; PMCID: PMC4422520.
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PLoS One. 2015 May 06;10(5):e0126669. doi: 10.1371/journal.pone.0126669. eCollection 2015.

Molecular structure-affinity relationship of bufadienolides and human serum albumin in vitro and molecular docking analysis.

PloS one

Jing Zhou, Guodi Lu, Honglan Wang, Junfeng Zhang, Jinao Duan, Hongyue Ma, Qinan Wu

Affiliations

  1. Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, PR China.
  2. Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, PR China; Gansu University of Traditional Chinese Medicine, Lanzhou, PR China.
  3. College of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China.

PMID: 25946161 PMCID: PMC4422520 DOI: 10.1371/journal.pone.0126669

Abstract

The development of bufadienolides as anti-tumor agents is limited due to poor pharmacokinetic properties regarding drug half-lives and toxicity in vivo. These serious factors might be improved by increasing the drug/albumin-binding ratio. This study therefore investigated the relationship between the structural properties of nine bufadienolides and their affinities for human serum albumin (HSA) by a fluorescence spectroscopy-based analysis and molecular docking. Fluorescence quenching data showed that the interaction of each bufadienolide with HSA formed a non-fluorescent complex, while thermodynamic parameters revealed negative ΔS and ΔH values, corresponding to changes in enthalpy and entropy, respectively. The structural differences between the various bufadienolides markedly influenced their binding affinity for HSA. With the exception of a C = O bond at the C12 position that decreased the binding affinity for HSA, other polar groups tended to increase the affinity, especially a hydroxyl (OH) group at assorted bufadienolide sites. The rank order of binding affinities for drugs with tri-hydroxyl groups was as follows: 11-OH > 5-OH > 16-OH; in addition, 16-acetoxy (OAc), 10-aldehyde and 14-epoxy constituents notably enhanced the binding affinity. Among these groups, 11-OH and 16-acetyl were especially important for a seamless interaction between the bufadienolides and HSA. Furthermore, molecular docking analysis revealed that either an 11-OH or a 16-OAc group spatially close to a five-membered lactone ring significantly facilitated the anchoring of these compounds within site I of the HSA pocket via hydrogen bonding (H-bonding) with Tyr150 or Lys199, respectively. In summary, bufadienolide structure strongly affects binding with HSA, and 11-OH or 16-OAc groups improve the drug association with key amino acid residues. This information is valuable for the prospective development of bufadienolides with improved pharmacological profiles as novel anti-tumor drugs.

References

  1. Drug Metab Rev. 1976;5(1):43-140 - PubMed
  2. J Biol Chem. 1996 Jun 14;271(24):14067-72 - PubMed
  3. J Mol Biol. 2005 Oct 14;353(1):38-52 - PubMed
  4. J Pharm Biomed Anal. 2008 Mar 13;46(4):699-706 - PubMed
  5. Anal Chim Acta. 2008 Mar 10;610(2):224-31 - PubMed
  6. J Fluoresc. 2008 Mar;18(2):433-42 - PubMed
  7. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Dec 1;876(1):69-75 - PubMed
  8. PLoS One. 2010;5(1):e8834 - PubMed
  9. Mol Nutr Food Res. 2010 Jul;54 Suppl 2:S253-60 - PubMed
  10. Biochem Biophys Res Commun. 2010 Jul 30;398(3):444-9 - PubMed
  11. Zhong Xi Yi Jie He Xue Bao. 2011 Jul;9(7):768-74 - PubMed
  12. Eur J Med Chem. 2011 Sep;46(9):4344-53 - PubMed
  13. Bioorg Med Chem Lett. 2012 Jan 1;22(1):154-63 - PubMed
  14. Cardiovasc Toxicol. 2012 Mar;12(1):83-9 - PubMed
  15. Curr Med Chem. 2012;19(5):627-46 - PubMed
  16. Molecules. 2012;17(3):3114-47 - PubMed
  17. Exp Toxicol Pathol. 2012 Jul;64(5):417-23 - PubMed
  18. Spectrochim Acta A Mol Biomol Spectrosc. 2012 Nov;97:449-55 - PubMed
  19. Toxicol In Vitro. 2013 Feb;27(1):396-401 - PubMed
  20. Int J Mol Sci. 2014;15(3):3580-95 - PubMed
  21. Luminescence. 2014 Jun;29(4):314-31 - PubMed
  22. Biochemistry. 1981 May 26;20(11):3096-102 - PubMed
  23. Spectrochim Acta A Mol Biomol Spectrosc. 2015 Jan 25;135:410-6 - PubMed
  24. Adv Protein Chem. 1994;45:153-203 - PubMed
  25. Nat Prod Rep. 1998 Aug;15(4):397-413 - PubMed

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