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Biological activity of antitumoural MGBG: the structural variable

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Abstract

The present study aims at determining the structure-activity relationships (SAR’s) ruling the biological function of MGBG (methylglyoxal bis(guanylhydrazone)), a competitive inhibitor of S-adenosyl-l-methionine decarboxylase displaying anticancer activity, involved in the biosynthesis of the naturally occurring polyamines spermidine and spermine. In order to properly understand its biochemical activity, MGBG’s structural preferences at physiological conditions were ascertained, by quantum mechanical (DFT) calculations.

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Abbreviations

CsA:

Cyclosporin A

ΔΨ:

Electrical membrane potential

DFT:

Density functional theory

FCCP:

Carbonyl cyanide-p-trifluorometoxyphenylhydrazone

MGBG:

Methylglyoxal bis(guanylhydrazone)

MPT:

Mitochondrial permeability transition

PCM:

Polarised continuum model

RLM:

Rat liver mitochondria

SAMDC:

S-Adenosyl-l-methionine decarboxylase

SCRF:

Self-consistent reaction field

SD:

Standard deviation

SSAT:

Spermidine–spermine acetyltranferase

TPP+ :

Tetraphenylphosphonium cation

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Acknowledgments

Work performed within the COST Action 922 from the European Science Foundation. RC acknowledges financial support from the Portuguese Foundation for Science and Technology—PhD fellowship SFRH/BD/16520/2004. The authors also thank Sandoz Pharma, Basel (Switzerland) for having supplied cyclosporin A.

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Authors and Affiliations

  1. Research Unit “Química-Física Molecular”, University of Coimbra, Coimbra, Portugal

    M. P. M. Marques, F. P. S. C. Gil & R. Calheiros

  2. Biochemistry Department, Faculty of Science and Technology, University of Coimbra, Ap.3126, 3001-401, Coimbra, Portugal

    M. P. M. Marques

  3. CEMDRX, Physics Department, University of Coimbra, Coimbra, Portugal

    F. P. S. C. Gil

  4. Department of Biological Chemistry, University of Padua, Institute of Neurosciences of the CNR, Padua, Italy

    V. Battaglia, A. M. Brunati & A. Toninello

  5. Department of Biochemical Science “A. Rossi Fanelli”, Institute of Molecular Biology and Pathology, University of Rome “La Sapienza” and CNR, Rome, Italy

    E. Agostinelli

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  1. M. P. M. Marques
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  2. F. P. S. C. Gil
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  3. R. Calheiros
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  4. V. Battaglia
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  6. E. Agostinelli
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  7. A. Toninello
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Correspondence to M. P. M. Marques.

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Marques, M.P.M., Gil, F.P.S.C., Calheiros, R. et al. Biological activity of antitumoural MGBG: the structural variable. Amino Acids 34, 555–564 (2008). https://doi.org/10.1007/s00726-007-0009-2

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  • DOI: https://doi.org/10.1007/s00726-007-0009-2

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