Skip to main content

Advertisement

SpringerLink
Log in

Thermodynamics of Solution, Interaction with Calf Thymus DNA and Anticancer Activity of Phenylhydrazone Derivatives

  • Published:
Journal of Solution Chemistry Aims and scope Submit manuscript

Abstract

The solubilities in water (W) and in 3 mol⋅L−1 aqueous acetonitrile at 298.15 K of thiophene-2-, furan-2- and pyrrole-2-carboxaldehyde phenylhydrazone along with their nitro and 2,4-dinitro derivatives, referred to as PCT, PCF, PCP, NPCT, NPCF, NPCP, DPCT, DPCF and DPCP, respectively, are reported. The standard Gibbs energy of transfer from W to solvent mixtures (\(\Delta G^{\mathrm{transf}}_{\mathrm{W-mix}}\)) was estimated for each solute. The results indicate that the transfer process for all systems is a spontaneous process. Calculations under the scaled-particle theory suggest that the work of cavity creation (ΔΔG c), which is associated with the transfer of the phenylhydrazone from W to mix, dominates the magnitude of \(\mathrm {\Delta} G^{\mathrm{transf}}_{\mathrm{W-mix}}\). UV spectroscopic measurements suggest that these compounds bind calf thymus(CT)-DNA via intercalation mode in a buffer–3 mol⋅L−1 acetonitrile solution. The binding constant (K b) depends on the nitro-substitution on the phenyl moiety and the electronegativity of the heteroatom in the heterocyclic ring. The corresponding Gibbs energy of binding (\(\Delta G_{\mathrm{DNA-B}}^{0}\)) of phenylhydrazone derivatives to CT-DNA shows a marked dependence with ΔΔG c. The anticancer activity on human breast cancer cell lines MDA-231, MDA-435 and HT-29 human colon adenocarcinoma cell line was evaluated for the compounds NPCT, NPCF, DPCT and PCT.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Rollas, S., Küçükgüzel, S.G.: Biological activities of hydrazone derivatives. Molecules 12(8), 1910–1939 (2007)

    Article  CAS  Google Scholar 

  2. Kalinowski, D.S., Richardson, D.R.: The evolution of iron chelators for the treatment of iron overload disease and cancer. Pharmacol. Rev. 57(4), 547–583 (2005)

    Article  CAS  Google Scholar 

  3. Morgan, L.R., Thangaraj, K., LeBlanc, B., Rodgers, A., Wolford, L.T., Hooper, C.L., Fan, D., Jursic, B.S.: Design synthesis, and anticancer properties of 4,4′-dihydroxybenzophenone-2,4-dinitrophenylhydrazone and analogues. J. Med. Chem. 46(21), 4552–4563 (2003)

    Article  CAS  Google Scholar 

  4. Morgan, L.R., Jursic, B.S., Hooper, C.L., Neumann, D.M., Thangaraj, K., LeBlanc, B.: Anticancer activity for 4,4′-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) analogues and their abilities to interact with lymphoendothelial cell surface markers. Bioorg. Med. Chem. Lett. 12(23), 3407–3411 (2002)

    Article  CAS  Google Scholar 

  5. Sagiraju, S., Jursic, B.S.: NMR spectroscopic study of cyclodextrin inclusion complexes with A-007 prodrugs. Carbohydr. Res. 343(7), 1180–1190 (2008)

    Article  CAS  Google Scholar 

  6. Alvarado, Y.J., Caldera-Luzardo, J., Ferrer-Amado, G., Manzilla-Labarca, V., Michelena, E.: Determination of the apparent molar refraction and partial molar volume at infinite dilution of thiophene-pyrrole- and furan-2-carboxaldehyde phenylhydrazone derivatives in acetonitrile at 293.15 K. J. Solution Chem. 36(1), 1–11 (2007)

    Article  CAS  Google Scholar 

  7. Hollósy, F., Lóránd, T., Örfi, L., Erös, D., Kéri, G., Idei, M.: Evaluation of hydrofobicity and antitumor activity of a molecule library of Mannich ketones of cycloalkanones. J. Liq. Chromatogr. R. T. 25(7), 1129–1143 (2002)

    Article  Google Scholar 

  8. Wang, H., Ben-Naim, A.: A possible involvement of solvent-induced interactions in drug design. J. Med. Chem. 39(7), 1531–1539 (1996)

    Article  CAS  Google Scholar 

  9. Miyamoto, S., Kollman, P.A.: What determines the strength of noncovalent association of ligands to proteins in aqueous solution? Proc. Natl. Acad. Sci. USA 90(18), 8402–8406 (1993)

    Article  CAS  Google Scholar 

  10. Pierotti, R.A.: A scaled particle theory of aqueous and nonaqueous solutions. Chem. Rev. 76(6), 717–726 (1976)

    Article  CAS  Google Scholar 

  11. Graziano, G.: Solvation thermodynamics of water in nonpolar organic solvents indicate the occurrence of nontraditional hydrogen bonds. J. Phys. Chem. B 109(2), 981–985 (2005)

    Article  CAS  Google Scholar 

  12. Graziano, G.: Hydration thermodynamics of N-methylacetamide. J. Phys. Soc. Jpn. 69(11), 3720–3725 (2000)

    Article  CAS  Google Scholar 

  13. Liu, Z., Weng, W., Bookchin, R.M., Lew, V.L., Ferrone, F.A.: Free energy of sickle hemoglobin polymerization: A scaled-particle treatment for use with dextran as a crowding agent. Biophys. J. 94(9), 3629–3634 (2008)

    Article  CAS  Google Scholar 

  14. Qu, X., Chaires, J.B.: Contrasting hydration changes for ethidium and daunomycin binding to DNA. J. Am. Chem. Soc. 121(11), 2649–2650 (1999)

    Article  CAS  Google Scholar 

  15. Markarian, S.A., Asatryan, A.M., Grigoryan, K.R., Sargsyan, H.R.: Effect of diethylsulfoxide on the thermal denaturation of DNA. Biopolymers 82(1), 1–5 (2006)

    Article  CAS  Google Scholar 

  16. Bakó, I., Megyes, T., Grósz, T., Pálinkás, G., Dore, J.: Structural investigation of water-acetonitrile mixtures: Small-angle and wide-angle neutron diffraction study compared to molecular dynamics simulation. J. Mol. Liq. 125(2–3), 174–180 (2006)

    Google Scholar 

  17. Soscún, H., Alvarado, Y., Hernández, J., Hernández, P., Atencio, R., Hinchliffe, A.: Experimental and theoretical determination of the dipole polarizability of dibenzothiophene. J. Phys. Org. Chem. 14(10), 709–715 (2001)

    Article  Google Scholar 

  18. Alvarado, Y.J., Cubillán, N.H., Labarca, P., Karam, A., Arrieta, F., Castellano, O., Soscún, H.: Dipole polarizability of the pyrazabole molecule in solution. J. Phys. Org. Chem. 15(12), 835–843 (2002)

    Article  CAS  Google Scholar 

  19. Alvarado, Y.J., Cubillán, N.H., Labarca, P., Karam, A., Arrieta, F., Castellano, O., Soscún, H.: Static and dynamic dipole polarizabilities of 2- and 3-methylthiophenes in solution: experimental and theoretical determination. J. Phys. Org. Chem. 15(3), 154–164 (2002)

    Article  CAS  Google Scholar 

  20. Alvarado, Y.J., Labarca, P., Cubillán, N., Osorio, E., Karam, A.: Solvent effect on electronic polarizability of benzonitrile. Z. Naturforsch. 58a(2), 68–74 (2003)

    Google Scholar 

  21. Alvarado, Y.J., Caldera-Luzardo, J., De La Cruz, C., Ferrer-Amado, G., Michelena, E., Silva, P.: Volumetric electric, and magnetic properties of thioxanthen-9-one in aprotic solvents as revealed by high-precision densitometry, high-accuracy refractometry and magnetic susceptibility measurements and by DFT calculations. J. Solution Chem. 35(1), 29–49 (2006)

    Article  CAS  Google Scholar 

  22. Marmur, J.: A procedure for the isolation of DNA from microorganisms. J. Mol. Biol. 3, 208–218 (1961)

    Article  CAS  Google Scholar 

  23. Reichmann, M.E., Rice, S.A., Thomas, C.A., Doty, P.: A further examination of the molecular weight and size of desoxypentose nucleic acid. J. Am. Chem. Soc. 76(11), 3047–3053 (1954)

    Article  CAS  Google Scholar 

  24. Zielenkiewicz, W., Golankiewicz, B., Perlovich, G.L., Kozbial, M.: Aqueous solubilities infinite dilution activity coefficients and octanol-water partition coefficients of tricyclic analogs of Acyclovir. J. Solution Chem. 28(6), 731–745 (1999)

    Article  CAS  Google Scholar 

  25. Segatin, N., Klofutar, C.: Thermodynamics of solution of some alkyl acetates in water. Monatsh. Chem. 132(12), 1451–1462 (2001)

    Article  CAS  Google Scholar 

  26. Graziano, G.: On the solubility of aliphatic hydrocarbons in 7 M aqueous urea. J. Phys. Chem. B 105(13), 2632–2637 (2001)

    Article  CAS  Google Scholar 

  27. Ben-Naim, A.: Solvation Thermodynamics. Springer, Amsterdam (1987)

    Google Scholar 

  28. Graziano, G.: Size and temperature dependence of hydrocarbon solubility in concentrated aqueous solutions of urea and guanidine hydrochroride. Can. J. Chem. 80(4), 388–400 (2002)

    Article  CAS  Google Scholar 

  29. Graziano, G.: Cavity size distribution in the interior of globular proteins. Chem. Phys. Lett. 434(4–6), 316–319 (2007)

    Article  CAS  Google Scholar 

  30. Stolypin, V.F., Mishustin, A.L.: Calculation of the contribution from van der Waals interactions to the thermodynamic properties of binary mixtures of dipolar aprotic solvents. Russ. J. Phys. Chem. 61, 1703–1705 (1987)

    Google Scholar 

  31. Stolypin, V.F.: Complexation of 18-crown-ether with acetonitrile. Russ. J. Phys. Chem. 71, 1969–1973 (1997)

    Google Scholar 

  32. Riddle, F., Fowkes, F.: Spectral shifts in acid-base chemistry. 1. van der Waals contributions to acceptor numbers. J. Am. Chem. Soc. 112(9), 3259–3264 (1990)

    Article  CAS  Google Scholar 

  33. Quin, Y., Prausnitz, J.M.: Solubilities in ionic liquids and molten salts from a simple perturberd-hard-sphere theory. Ind. Eng. Chem. Res. 45(16), 5518–5523 (2006)

    Article  Google Scholar 

  34. Gagliardi, L.G., Castells, C.B., Rafols, C., Roses, M., Bosch, E.: Static dielectric constants of acetonitrile/water mixtures at different temperatures and Debye–Huckel A and a 0 B parameters for activity coefficients. J. Chem. Eng. Data 52(3), 1103–1107 (2007)

    Article  CAS  Google Scholar 

  35. Lide, D.R. (ed.): CRC Handbook of Chemistry and Physics, 90th edn. CRC Press, Boca Raton (2009)

    Google Scholar 

  36. Alvarado, Y., Álvarez Mon, M., Baricelli, J., Caldera-Luzardo, J., Cubillán, N., Ferrer-Amado, G., Hassanhi, M., Marrero-Ponce, Y., Mancilla, V., Rocafull, M., San Antonio-Sánchez, M., Ojeda-Andara, J., Thomas, L.: Solubility of thiophene-, furan- and pyrrole-2-carboxaldehyde phenylhydrazone derivatives in 2.82 mol⋅L−1 aqueous DMSO at 298.15 K, inhibition of lymphoproliferation and tubulin polymerization: A study based on the scaled particle theory. J. Solution Chem. 39(8), 1099–1112 (2010)

    Article  CAS  Google Scholar 

  37. Ababneh, A.M., Large, C., Georghiou, S.: Solvation of nucleosides in aqueous mixtures of organic solvents: Relevance to DNA open basepairs. Biophys. J. 85(2), 1111–1127 (2003)

    Article  CAS  Google Scholar 

  38. Hertzberg, R.P., Dervan, P.B.: Cleavage of double helical DNA by methidium-propyl-EDTA-iron(II). J. Am. Chem. Soc. 104(1), 313–315 (1982)

    Article  CAS  Google Scholar 

  39. Nakayama, G.R., Caton, M.C., Nova, M.P., Parandoosh, Z.: Assessment of the Alamar Blue assay for cellular growth and viability in vitro. J. Immunol. Methods 204(2), 205–208 (1997)

    Article  CAS  Google Scholar 

  40. Alvarado, Y.J., Cubillán, N.: Manuscript in preparation

  41. Singh, D.K., Srivastava, S.K., Ojha, A.K., Asthana, B.P.: Vibrational study of thiophene and its solvation in two polar solvents, DMSO and methanol by Raman spectroscopy combined with ab initio and DFT calculations. J. Mol. Struct. 892(1–3), 384–391 (2008)

    Article  CAS  Google Scholar 

  42. He, X.-Q., Lin, Q.-Y., Hu, R.-D., Lu, X.-H.: Synthesis characterization and DNA-binding studies on La(III) and Ce(III) complexes containing ligand of N-phenyl-2-pyridinecarboxamide. Spectrochim. Acta A 68(1), 184–190 (2007)

    Article  Google Scholar 

  43. Lawrence, D., Vaidyanathan, V., Nair, B.U.: Synthesis characterization and DNA binding studies of two mixed ligand complexes of ruthenium(II). J. Inorg. Biochem. 100(7), 1244–1251 (2006)

    Article  CAS  Google Scholar 

  44. Yin, Z., Qian, H., Li, H., Hu, J., Zhang, C.: Thiophene-2-carbaldehyde 2,4-dinitrophenylhydrazone. Acta Crystallogr. E 64(12), o2421 (2008)

    Article  Google Scholar 

  45. Librando, L., Alparone, A.: The role of electronic properties to the mutagenic activity of 1,6- and 3,6-dinitrobenzo[a]pyrene isomers. J. Hazard. Mater. 161(2–3), 1338–1346 (2009)

    Article  CAS  Google Scholar 

  46. Qiao, Y.-H., Lin, H., Shao, J., Lin, H.-K.: A highly selective naked-eye colorimetric sensor for acetate ion based on 1,10-phenanthroline-2,9-dicarboxyaldehyde-di-(p-substitutedphenyl-hydrazone). Spectrochim. Acta A 72(2), 378–381 (2009)

    Article  Google Scholar 

  47. Shao, J., Qiao, Y., Lin, H., Lin, H.: A C3-symmetric colorimetric anion sensor bearing hydrazone groups as binding sites. Spectrochim. Acta A 71(5), 1736–1740 (2009)

    Article  Google Scholar 

  48. Shang, X.-F., Xu, X.-F.: The anion recognition properties of hydrazone derivatives containing anthracene. BioSystems 96(2), 165–171 (2009)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratorio de Electrónica Molecular (LEM), Departamento de Química, Facultad Experimental de Ciencias, La Universidad del Zulia, Ap. 526, Grano de Oro, Módulo No. 2, Maracaibo, Estado Zulia, República Bolivariana de Venezuela

    Ysaías J. Alvarado, José Caldera-Luzardo, Néstor Cubillán, Victoria Mancilla, José Ojeda-Andara & Miguel Morales-Toyo

  2. Departamento de Investigación y Tecnología de los Materiales y Ambiente (DITeMA), Instituto Venezolano de Investigaciones Científicas (IVIC), Maracaibo, Estado Zulia, República Bolivariana de Venezuela

    Ysaías J. Alvarado, Gladys Ferrer-Amado & Joan Vera-Villalobos

  3. Laboratorio de Fisiología Molecular, Centro de Biofísica y Bioquímica, Instituto Venezolano de Investigaciones Científicas (IVIC), Carretera Panamericana Km 11, Apartado 21827, Caracas, 1020-A, República Bolivariana de Venezuela

    Joanna Baricelli, Miguel A. Rocafull & Luz E. Thomas

  4. Laboratorio de Diseño de Fármacos, Departamento de Farmacia, Centro de Química Bio-activa, Universidad Central de las Villas, Santa Clara, Cuba

    Yovani Marrero-Ponce

Authors
  1. Ysaías J. Alvarado
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joanna Baricelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. José Caldera-Luzardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Néstor Cubillán
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gladys Ferrer-Amado
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yovani Marrero-Ponce
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Victoria Mancilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Miguel A. Rocafull
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. José Ojeda-Andara
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luz E. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Joan Vera-Villalobos
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Miguel Morales-Toyo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ysaías J. Alvarado.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alvarado, Y.J., Baricelli, J., Caldera-Luzardo, J. et al. Thermodynamics of Solution, Interaction with Calf Thymus DNA and Anticancer Activity of Phenylhydrazone Derivatives. J Solution Chem 40, 26–39 (2011). https://doi.org/10.1007/s10953-010-9635-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10953-010-9635-5

Keywords

Search

Navigation