Interaction of mitoxantrone with human serum albumin: Spectroscopic and molecular modeling studies

Shahper N. Khan, Barira Islam, Ragothaman Yennamalli, Abdullah Sultan, Naidu Subbarao, Asad U. Khan

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Mitoxantrone (MTX) is a clinically used antitumor anthracycline, which is made available to the target tissues by transport protein human serum albumin (HSA). Being less toxic unlike other member of this family, its binding characteristics are therefore of immense interest. The circular dichroism (CD), fluorescence and Fourier transform infrared (FTIR) spectroscopies were employed to elucidate the mode and the mechanism for this interaction. MTX binding is characterized by one high affinity binding site with the association constants of the order of 105. Correlation between stability of N-MTX (drug bound N form of HSA) and B-MTX (drug bound B form of HSA) complexes with drug distribution has been discussed. The molecular distance, r, between donor (HSA) and acceptor (MTX) was estimated according to Forster's theory of non-radiation energy transfer. The features of MTX induced structural perturbation of human serum albumin (HSA) has been studied in detail by CD and FTIR analysis. Domain I was assigned to possess high affinity binding site for MTX. Molecular docking showed that the MTX binds HSA to a non-classical drug binding site. The binding dynamics was expounded by synchronous fluorescence, thermodynamic parameters and molecular modeling, which entails that hydrophobic interactions, hydrogen bonding and electrostatic forces, stabilizes the interaction.

LanguageEnglish
Pages371-382
Number of pages12
JournalEuropean Journal of Pharmaceutical Sciences
Volume35
Issue number5
Early online date13 Aug 2008
DOIs
Publication statusPublished - 18 Dec 2008
Externally publishedYes

Fingerprint

Mitoxantrone
Serum Albumin
Binding Sites
Circular Dichroism
Pharmaceutical Preparations
Fluorescence
Poisons
Anthracyclines
Energy Transfer
Fourier Analysis
Fourier Transform Infrared Spectroscopy
Hydrogen Bonding
Static Electricity
Hydrophobic and Hydrophilic Interactions
Thermodynamics
Carrier Proteins

Cite this

Khan, Shahper N. ; Islam, Barira ; Yennamalli, Ragothaman ; Sultan, Abdullah ; Subbarao, Naidu ; Khan, Asad U. / Interaction of mitoxantrone with human serum albumin : Spectroscopic and molecular modeling studies. In: European Journal of Pharmaceutical Sciences. 2008 ; Vol. 35, No. 5. pp. 371-382.
@article{3f918e1a09bf43ed931b7c9d6fa70692,
title = "Interaction of mitoxantrone with human serum albumin: Spectroscopic and molecular modeling studies",
abstract = "Mitoxantrone (MTX) is a clinically used antitumor anthracycline, which is made available to the target tissues by transport protein human serum albumin (HSA). Being less toxic unlike other member of this family, its binding characteristics are therefore of immense interest. The circular dichroism (CD), fluorescence and Fourier transform infrared (FTIR) spectroscopies were employed to elucidate the mode and the mechanism for this interaction. MTX binding is characterized by one high affinity binding site with the association constants of the order of 105. Correlation between stability of N-MTX (drug bound N form of HSA) and B-MTX (drug bound B form of HSA) complexes with drug distribution has been discussed. The molecular distance, r, between donor (HSA) and acceptor (MTX) was estimated according to Forster's theory of non-radiation energy transfer. The features of MTX induced structural perturbation of human serum albumin (HSA) has been studied in detail by CD and FTIR analysis. Domain I was assigned to possess high affinity binding site for MTX. Molecular docking showed that the MTX binds HSA to a non-classical drug binding site. The binding dynamics was expounded by synchronous fluorescence, thermodynamic parameters and molecular modeling, which entails that hydrophobic interactions, hydrogen bonding and electrostatic forces, stabilizes the interaction.",
keywords = "Antitumor, Drug binding pocket, Fluorescence resonance energy transfer, Molecular modeling",
author = "Khan, {Shahper N.} and Barira Islam and Ragothaman Yennamalli and Abdullah Sultan and Naidu Subbarao and Khan, {Asad U.}",
year = "2008",
month = "12",
day = "18",
doi = "10.1016/j.ejps.2008.07.010",
language = "English",
volume = "35",
pages = "371--382",
journal = "European Journal of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "Elsevier",
number = "5",

}

Interaction of mitoxantrone with human serum albumin : Spectroscopic and molecular modeling studies. / Khan, Shahper N.; Islam, Barira; Yennamalli, Ragothaman; Sultan, Abdullah; Subbarao, Naidu; Khan, Asad U.

In: European Journal of Pharmaceutical Sciences, Vol. 35, No. 5, 18.12.2008, p. 371-382.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interaction of mitoxantrone with human serum albumin

T2 - European Journal of Pharmaceutical Sciences

AU - Khan, Shahper N.

AU - Islam, Barira

AU - Yennamalli, Ragothaman

AU - Sultan, Abdullah

AU - Subbarao, Naidu

AU - Khan, Asad U.

PY - 2008/12/18

Y1 - 2008/12/18

N2 - Mitoxantrone (MTX) is a clinically used antitumor anthracycline, which is made available to the target tissues by transport protein human serum albumin (HSA). Being less toxic unlike other member of this family, its binding characteristics are therefore of immense interest. The circular dichroism (CD), fluorescence and Fourier transform infrared (FTIR) spectroscopies were employed to elucidate the mode and the mechanism for this interaction. MTX binding is characterized by one high affinity binding site with the association constants of the order of 105. Correlation between stability of N-MTX (drug bound N form of HSA) and B-MTX (drug bound B form of HSA) complexes with drug distribution has been discussed. The molecular distance, r, between donor (HSA) and acceptor (MTX) was estimated according to Forster's theory of non-radiation energy transfer. The features of MTX induced structural perturbation of human serum albumin (HSA) has been studied in detail by CD and FTIR analysis. Domain I was assigned to possess high affinity binding site for MTX. Molecular docking showed that the MTX binds HSA to a non-classical drug binding site. The binding dynamics was expounded by synchronous fluorescence, thermodynamic parameters and molecular modeling, which entails that hydrophobic interactions, hydrogen bonding and electrostatic forces, stabilizes the interaction.

AB - Mitoxantrone (MTX) is a clinically used antitumor anthracycline, which is made available to the target tissues by transport protein human serum albumin (HSA). Being less toxic unlike other member of this family, its binding characteristics are therefore of immense interest. The circular dichroism (CD), fluorescence and Fourier transform infrared (FTIR) spectroscopies were employed to elucidate the mode and the mechanism for this interaction. MTX binding is characterized by one high affinity binding site with the association constants of the order of 105. Correlation between stability of N-MTX (drug bound N form of HSA) and B-MTX (drug bound B form of HSA) complexes with drug distribution has been discussed. The molecular distance, r, between donor (HSA) and acceptor (MTX) was estimated according to Forster's theory of non-radiation energy transfer. The features of MTX induced structural perturbation of human serum albumin (HSA) has been studied in detail by CD and FTIR analysis. Domain I was assigned to possess high affinity binding site for MTX. Molecular docking showed that the MTX binds HSA to a non-classical drug binding site. The binding dynamics was expounded by synchronous fluorescence, thermodynamic parameters and molecular modeling, which entails that hydrophobic interactions, hydrogen bonding and electrostatic forces, stabilizes the interaction.

KW - Antitumor

KW - Drug binding pocket

KW - Fluorescence resonance energy transfer

KW - Molecular modeling

UR - http://www.scopus.com/inward/record.url?scp=55949121032&partnerID=8YFLogxK

U2 - 10.1016/j.ejps.2008.07.010

DO - 10.1016/j.ejps.2008.07.010

M3 - Article

VL - 35

SP - 371

EP - 382

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

IS - 5

ER -