Skip to main content
Log in

Design, synthesis and investigation of the interaction behavior between two acridone derivatives, 8-chloro acridone and nitrile cyanide acridone with calf thymus DNA, by different spectroscopic techniques

  • Original Paper
  • Published:
Journal of the Iranian Chemical Society Aims and scope Submit manuscript

Abstract

Evaluating the binding interaction between biomacromolecules and various chemical compounds is one of the most biologically researched topics. The present experimental study attempted to investigate the binding interaction between two types of acridone derivative, namely 8-chloro acridone (CA) and nitrile cyanide acridone (NCA) as antineoplastic agents and calf thymus DNA (ctDNA) by applying various spectroscopic techniques. The binding interactions were first characterized by fluorescence quenching experiments, and it was demonstrated that NCA had higher affinity to ctDNA and bound to it more tightly. Further analysis indicated that the quenching process between CA and ctDNA was controlled by a dynamic mechanism, while the dominant process in ctDNA–NCA interaction was static. Analysis of thermodynamic parameters showed that hydrophobic forces played a key role in the interaction between ctDNA and CA, whereas ctDNA–NCA complex was mainly stabilized by van der Waals interactions. In terms of the latter interaction, external binding also contributed to the stabilization of the formed complex. On the basis of RLS results, we concluded that CA had stronger potential toxicity on ctDNA than NCA. Fluorescence competition studies aimed at uncovering the mode of binding and indicated that CA and NCA probably intercalated into ctDNA. Thermal denaturation studies confirmed the displacement experiments and showed that CA brought about a stronger effect on the ctDNA stabilization. Data gathered by spectroscopy studies were further supported by viscosity experiments. These studies also showed that CA and NCA intercalated into ctDNA by a non-classical and classical mode, respectively. The results of circular dichroism experiments revealed no considerable conformational transition occurred in ctDNA upon the binding interactions and ctDNA remained in B-form. Based on the spectroscopic results and the binding affinity of CA to double-strand and single-strand ctDNA, we inferred that although CA predominantly intercalated into ctDNA, a small population of its molecules might bind to the grooves of ctDNA. In case of NCA, all the experimental results confirmed that NCA molecules intercalated into ctDNA by a classical mode.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  1. S.R. Wente, M.P. Rout, The nuclear pore complex and nuclear transport. Cold Spring Harbor Perspect. Biol. 2, a000562 (2010)

    Article  CAS  Google Scholar 

  2. Y. Sakiyama, R. Panatala, R.Y. Lim, Structural dynamics of the nuclear pore complex. in Seminars in Cell and Developmental Biology: 2017. (Elsevier, Amsterdam, 2017), pp. 27–33

    Article  CAS  Google Scholar 

  3. M. Capelson, Nuclear pores and the genome. in Nuclear Architecture and Dynamics, ed. by C. Lavelle, J.-M. Victor (Elsevier, Amsterdam, 2018), pp. 369–385

    Chapter  Google Scholar 

  4. M. Sirajuddin, S. Ali, A. Badshah, Drug–DNA interactions and their study by UV–visible, fluorescence spectroscopies and cyclic voltametry. J. Photochem. Photobiol., B 124, 1–19 (2013)

    Article  CAS  Google Scholar 

  5. X. Zhang, L. Chen, X.-C. Fei, Y.-S. Ma, H.-W. Gao, Binding of PFOS to serum albumin and DNA: insight into the molecular toxicity of perfluorochemicals. BMC Mol. Biol. 10(1), 16 (2009)

    Article  Google Scholar 

  6. J. Sheng, J. Gan, Z. Huang, Structure-based DNA-targeting strategies with small molecule ligands for drug discovery. Med. Res. Rev. 33(5), 1119–1173 (2013)

    Article  CAS  Google Scholar 

  7. C.T. Winston, D.L. Boger, Sequence-selective DNA recognition: natural products and nature’s lessons. Chem. Biol. 11(12), 1607–1617 (2004)

    Article  Google Scholar 

  8. N. Narayanaswamy, S. Das, P.K. Samanta, K. Banu, G.P. Sharma, N. Mondal, S.K. Dhar, S.K. Pati, T. Govindaraju, Sequence-specific recognition of DNA minor groove by an NIR-fluorescence switch-on probe and its potential applications. Nucleic Acids Res. 43(18), 8651–8663 (2015)

    Article  CAS  Google Scholar 

  9. I. Haq, Thermodynamics of drug–DNA interactions. Arch. Biochem. Biophys. 403(1), 1–15 (2002)

    Article  CAS  Google Scholar 

  10. Y.M. Delahoussaye, M.P. Hay, F.B. Pruijn, W.A. Denny, J.M. Brown, Improved potency of the hypoxic cytotoxin tirapazamine by DNA-targeting. Biochem. Pharmacol. 65(11), 1807–1815 (2003)

    Article  CAS  Google Scholar 

  11. K.R. Fox, M.J. Waring, DNA structural variations produced by actinomycin and distamycin as revealed by DNAase I footprinting. Nucleic Acids Res. 12(24), 9271–9285 (1984)

    Article  CAS  Google Scholar 

  12. A. Guttman, N. Cooke, Capillary gel affinity electrophoresis of DNA fragments. Anal. Chem. 63(18), 2038–2042 (1991)

    Article  CAS  Google Scholar 

  13. V. Yerragunta, E.S. Reddy, M. Kishore, H.O.P. Rao, A. Sadia, A. Saba, S.K. Fatima, A Review on Acridone Derivatives and its Importance. PharmaTutor 3(10), 27–29 (2015)

    CAS  Google Scholar 

  14. P. Belmont, J. Bosson, T. Godet, M. Tiano, Acridine and acridone derivatives, anticancer properties and synthetic methods: where are we now? Anti-Cancer Agents Med. Chem. (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 7(2), 139–169 (2007)

    Article  CAS  Google Scholar 

  15. V.R. Prasad, J.V. Rao, R. Giri, N. Sathish, S.S. Kumar, Y. Mayur, Chloro acridone derivatives as cytotoxic agents active on multidrug-resistant cell lines and their duplex DNA complex studies by electrospray ionization mass spectrometry. Chem. Biol. Interact. 176(2–3), 212–219 (2008)

    Article  CAS  Google Scholar 

  16. M.O. Anderson, J. Sherrill, P.B. Madrid, A.P. Liou, J.L. Weisman, J.L. DeRisi, R.K. Guy, Parallel synthesis of 9-aminoacridines and their evaluation against chloroquine-resistant Plasmodium falciparum. Bioorg. Med. Chem. 14(2), 334–343 (2006)

    Article  CAS  Google Scholar 

  17. W.A. Denny, Acridine derivatives as chemotherapeutic agents. Curr. Med. Chem. 9(18), 1655–1665 (2002)

    Article  CAS  Google Scholar 

  18. A. Rescifina, C. Zagni, M.G. Varrica, V. Pistara, A. Corsaro, Recent advances in small organic molecules as DNA intercalating agents: synthesis, activity, and modeling. Eur. J. Med. Chem. 74, 95–115 (2014)

    Article  CAS  Google Scholar 

  19. P. Belmont, I. Dorange, Acridine/acridone: a simple scaffold with a wide range of application in oncology. Expert Opin. Ther. Pat. 18(11), 1211–1224 (2008)

    Article  CAS  Google Scholar 

  20. M. Rahimizadeh, M. Pordel, M. Bakavoli, Z. Bakhtiarpoor, A. Orafaie, Synthesis of imidazo [4, 5-a] acridones and imidazo [4, 5-a] acridines as potential antibacterial agents. Monatshefte für Chemie-Chemical Monthly 140(6), 633 (2009)

    Article  CAS  Google Scholar 

  21. H.A. Benesi, J. Hildebrand, A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons. J. Am. Chem. Soc. 71(8), 2703–2707 (1949)

    Article  CAS  Google Scholar 

  22. G. Zhang, Y. Zhang, Y. Zhang, Y. Li, Spectroscopic studies of cyanazine binding to calf thymus DNA with the use of ethidium bromide as a probe. Sens. Actuators B Chemical 182, 453–460 (2013)

    Article  CAS  Google Scholar 

  23. S. Afrin, Y. Rahman, T. Sarwar, M.A. Husain, A. Ali, M. Tabish, Molecular spectroscopic and thermodynamic studies on the interaction of anti-platelet drug ticlopidine with calf thymus DNA. Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 186, 66–75 (2017)

    Article  CAS  Google Scholar 

  24. C.Z. Huang, Y.F. Li, Resonance light scattering technique used for biochemical and pharmaceutical analysis. Anal. Chim. Acta 500(1–2), 105–117 (2003)

    Article  CAS  Google Scholar 

  25. Y. Wang, S. Bi, H. Zhou, T. Zhao, Resonance light scattering spectroscopy of procyanidin–CPB–DNA ternary system and its potential application. Spectrochim. Acta Part A Mol. Biomol. Spectrosc. 146, 255–260 (2015)

    Article  CAS  Google Scholar 

  26. H. Tajmir-Riahi, D. Agudelo, P. Bourassa, Nutrition, diet, the eye, and vision: molecular aspects of vitamin a binding proteins and their importance in vision, in Handbook of Nutrition, Diet and the Eye, ed. by V. Preedy (Elsevier, Amsterdam, 2014), pp. 577–586

    Chapter  Google Scholar 

  27. J. Xu, J.R. Knutson, Ultrafast fluorescence spectroscopy via upconversion: applications to biophysics. Methods Enzymol. 450, 159–183 (2008)

    Article  CAS  Google Scholar 

  28. J.B. Chaires, Energetics of drug–DNA interactions. Biopolym. Orig. Res. Biomol. 44(3), 201–215 (1997)

    CAS  Google Scholar 

  29. R. Perozzo, G. Folkers, L. Scapozza, Thermodynamics of protein–ligand interactions: history, presence, and future aspects. J. Recept. Signal Transduct. 24(1–2), 1–52 (2004)

    Article  CAS  Google Scholar 

  30. S. Phukan, S. Mitra, Fluorescence behavior of ethidium bromide in homogeneous solvents and in presence of bile acid hosts. J. Photochem. Photobiol., A 244, 9–17 (2012)

    Article  CAS  Google Scholar 

  31. I. Rouzina, V.A. Bloomfield, Heat capacity effects on the melting of DNA. 1. General aspects. Biophys. J. 77(6), 3242–3251 (1999)

    Article  CAS  Google Scholar 

  32. K.J. Breslauer, R. Frank, H. Blöcker, L.A. Marky, Predicting DNA duplex stability from the base sequence. Proc. Natl. Acad. Sci. 83(11), 3746–3750 (1986)

    Article  CAS  Google Scholar 

  33. S.G. Delcourt, R. Blake, Stacking energies in DNA. J. Biol. Chem. 266(23), 15160–15169 (1991)

    CAS  PubMed  Google Scholar 

  34. G. Khandelwal, J. Bhyravabhotla, A phenomenological model for predicting melting temperatures of DNA sequences. PLoS ONE 5(8), e12433 (2010)

    Article  Google Scholar 

  35. L. Strekowski, B. Wilson, Noncovalent interactions with DNA: an overview. Mutat. Res./Fund. Mol. Mech. Mutagen. 623(1), 3–13 (2007)

    Article  CAS  Google Scholar 

  36. P.U. Maheswari, M. Palaniandavar, DNA binding and cleavage properties of certain tetrammine ruthenium (II) complexes of modified 1, 10-phenanthrolines–effect of hydrogen-bonding on DNA-binding affinity. J. Inorg. Biochem. 98(2), 219–230 (2004)

    Article  Google Scholar 

Download references

Acknowledgements

The financial support of the Research Council of the Mashhad Branch, Islamic Azad University, is gratefully acknowledged. The authors also thank Dr. Ljungberg for the English editing.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jamshidkhan Chamani.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Askari, A., Entezari, A.A., Pordel, M. et al. Design, synthesis and investigation of the interaction behavior between two acridone derivatives, 8-chloro acridone and nitrile cyanide acridone with calf thymus DNA, by different spectroscopic techniques. J IRAN CHEM SOC 17, 135–149 (2020). https://doi.org/10.1007/s13738-019-01757-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13738-019-01757-5

Keywords

Navigation