Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH18133 > Fulltext
RESEARCH ARTICLE
Contents Vol 71(7)

Ab Initio and DFT Study on Cyclophosphamide: Anticancer and Immunomodulating Agents

Giuseppe Bruno
+ Author Affiliations
- Author Affiliations

Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Viale F. Stagno d’Alcontres, 98166, Messina, Italy. Email: gbruno@unime.it

Australian Journal of Chemistry 71(7) 511-523 https://doi.org/10.1071/CH18133
Submitted: 31 March 2018  Accepted: 02 June 2018   Published: 3 July 2018

Abstract

Cyclophosphamide is presently the most frequently used drug for antineoplastic chemotherapy. It has shown a great response in the treatment of human malignancies including leukemia, lymphoma, germ cell tumours, medulloblastomas, and carcinomas of the breast, lung, and cervix. Cyclophosphamide is also one of the most important immunosuppressive agents. This study investigates the quantum-chemical electronic properties of cyclophosphamide, as well as some of its metabolites, which are computed using ab-initio and DFT calculations. The interaction energy calculations between water molecules and the cyclophosphamide show how, in the solid state, the presence of water of crystallisation will make cyclophosphamide more stable over time. Atomic charges, dipole moment, frontier molecular orbitals, electrostatic potential isosurface, geometric parameters, and proton affinity on every nitrogen site enable the characterisation of the electronic properties and clearly illustrate the reactive sites that could be associated with this biologically important class of molecules.


References

[1]  A. J. Sasco, Biomed. Pharmacother. 2008, 62, 110.
         | Crossref | GoogleScholarGoogle Scholar |

[2]  World Cancer Report 2014 (Eds B. W. Stewart, C. P. Wild) 2014 (International Agency for Research on Cancer: Lyon).

[3]  P. K. Goyal, J. Integr. Oncol. 2012, 1, 1.

[4]  M. E. Colvin, J. C. Sasaki, N. L. Tran, Curr. Pharm. Des. 1999, 5, 645.

[5]  A. Gilman, F. S. Phillips, Sciences 1946, 103, 409.
         | Crossref | GoogleScholarGoogle Scholar |

[6]  H. Hackstein, A. W. Thomson, Nat. Rev. Immunol. 2004, 4, 24.
         | Crossref | GoogleScholarGoogle Scholar |

[7]  B. D. Kahan, Nat. Rev. Immunol. 2003, 3, 831.
         | Crossref | GoogleScholarGoogle Scholar |

[8]  F. J. Dumont, Curr. Opin. Investig. Drugs 2001, 2, 357.

[9]  C. P. J. Adair, H. J. Bagg, Ann. Surg. 1931, 93, 190.
         | Crossref | GoogleScholarGoogle Scholar |

[10]  M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr, J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian 09, Revision D.01 2009 (Gaussian, Inc.: Wallingford, CT).

[11]  A. D. Becke, J. Chem. Phys. 1993, 98, 5648.
         | Crossref | GoogleScholarGoogle Scholar |

[12]  C. Møller, S. Plesset, Phys. Rev. 1934, 46, 618.
         | Crossref | GoogleScholarGoogle Scholar |

[13]  F. Martin, H. Zipse, J. Comput. Chem. 2005, 26, 97.
         | Crossref | GoogleScholarGoogle Scholar |

[14]  H. S. Friedman, A. E. Pegg, S. P. Johnson, N. A. Loktionova, M. E. Dolan, P. Modrich, R. C. Moschel, R. Struck, T. P. Brent, S. Ludeman, N. Bullock, C. Kilborn, S. Keir, Q. Dong, D. D. Bigner, O. M. Colvin, Cancer Chemother. Pharmacol. 1999, 43, 80.
         | Crossref | GoogleScholarGoogle Scholar |

[15]  L. H. Fraiser, S. Kanekal, J. P. Kehrer, Drugs 1991, 42, 781.
         | Crossref | GoogleScholarGoogle Scholar |

[16]  A. Tyndall, M. Matucci-Cerinic, Expert Opin. Biol. Ther. 2003, 3, 1041.
         | Crossref | GoogleScholarGoogle Scholar |

[17]  F. Patti, S. Lo Fermo, Autoimmune Dis. 2011, 2011, 961702.
         | Crossref | GoogleScholarGoogle Scholar |

[18]  S. M. O’Brien, H. M. Kantarjian, J. Cortes, M. Beran, C. A. Koller, F. J. Giles, S. Lerner, M. J. Keating, Clin. Oncol. 2001, 19, 1414.
         | Crossref | GoogleScholarGoogle Scholar |

[19]  G. B. Bauer, L. F. Povirk, Nucleic Acids Res. 1997, 25, 1211.
         | Crossref | GoogleScholarGoogle Scholar |

[20]  T. K. H. Chang, G. F. Weber, C. L. Crespi, D. Waxman, J. Cancer Res. 1993, 53, 5629.

[21]  F. Allen, C. M. Bird, R. S. Rowland, P. R. Raithby, Acta Crystallogr. Sect. B 1997, 53, 696.
         | Crossref | GoogleScholarGoogle Scholar |

[22]  S. Garcia-Blanco, A. Perales, Acta Crystallogr. Sect. B 1972, 28, 2647.
         | Crossref | GoogleScholarGoogle Scholar |

[23]  P. G. Jones, H. Thonnessen, A. Fischer, I. Neda, R. Schmutzler, J. Engel, B. Kutscher, U. Niemeyer, Acta Crystallogr. Sect. C 1996, 52, 2359.
         | Crossref | GoogleScholarGoogle Scholar |

[24]  D. A. Adamiak, R. Kinas, W. Saenger, W. J. Stec, Angew. Chem. 1977, 89, 336.
         | Crossref | GoogleScholarGoogle Scholar |

[25]  F. H. Herbstein, R. E. Marsh, Acta Crystallogr. Sect. B 1998, 54, 677.
         | Crossref | GoogleScholarGoogle Scholar |

[26]  D. A. Adamiak, W. Saenger, R. Kinas, W. J. Stec, Z. Naturforsch. C: J. Biosci. 1977, 32, 672.

[27]  I. L. Karle, J. M. Karle, W. Egan, G. Zon, J. A. Brandt, J. Am. Chem. Soc. 1977, 99, 4803.
         | Crossref | GoogleScholarGoogle Scholar |

[28]  P. G. Jones, H. Thönnessen, A. Fischer, I. Neda, R. Schmutzler, J. Engel, B. Kutscher, U. Niemeyer, Acta Crystallogr. Sect. C 1996, 52, 2359.
         | Crossref | GoogleScholarGoogle Scholar |

[29]  P. Metrangolo, G. Resnati, Cryst. Growth Des. 2012, 12, 5835.
         | Crossref | GoogleScholarGoogle Scholar |

[30]  J. Bernstein, R. E. Davis, L. Shimoni, N. L. Chang, Angew. Chem. 1995, 107, 1689.
         | Crossref | GoogleScholarGoogle Scholar |

[31]  M. C. Etter, J. C. MacDonald, J. Bernstein, Acta Crystallogr. Sect. B 1990, 46, 256.
         | Crossref | GoogleScholarGoogle Scholar |

[32]  J. Sponer, J. Leszczynski, P. Hobza, Biopolymers 2001, 61, 3.
         | Crossref | GoogleScholarGoogle Scholar |

[33]  Y. Podolyan, L. Gorb, J. J. Leszczynski, J. Phys. Chem. A 2000, 104, 7346.
         | Crossref | GoogleScholarGoogle Scholar |

[34]  B. Giese, D. McNaughton, Phys. Chem. Chem. Phys. 2002, 4, 5161.
         | Crossref | GoogleScholarGoogle Scholar |

[35]  F. Greco, A. Liguori, G. Sindona, N. Uccella, J. Am. Chem. Soc. 1990, 112, 9092.
         | Crossref | GoogleScholarGoogle Scholar |

[36]  A. K. Chandra, M. T. Nguyen, T. Uchimaru, T. Zeegers-Huyskens, J. Phys. Chem. A 1999, 103, 8853.
         | Crossref | GoogleScholarGoogle Scholar |

[37]  H. M. Badawi, W. Z. Förner, Z. Naturforsch., B: J. Chem. Sci. 2012, 67b, 1305.

[38]  V. Kumar, G. Jain, S. Kishor, L. M. Ramaniah, Comput. Theor. Chem. 2011, 968, 18.
         | Crossref | GoogleScholarGoogle Scholar |

[39]  M. R. Bozorgmehr, J. Chamani, G. Moslehi, J. Biomol. Struct. Dyn. 2015, 33, 1669.
         | Crossref | GoogleScholarGoogle Scholar |