Studies on self-aggregation of anthracycline drugs by restrained molecular dynamics approach using nuclear magnetic resonance spectroscopy supported by absorption, fluorescence, diffusion ordered spectroscopy and mass spectrometry.

Abstract:

:Self-association, a process that competes with binding to DNA and formation of hetero-complexes, is studied in anticancer drugs 4'-epiadriamycin, adriamycin and daunomycin by proton nuclear magnetic resonance spectroscopy. The 2D nuclear Overhauser enhancement spectra yield several intra-molecular and inter-molecular inter-proton connectivities suggesting specific stacking patterns of aromatic chromophores in parallel and anti-parallel orientation. Absorption, emission and diffusion ordered spectroscopy demonstrate the formation of self-aggregates. Electron spray ionization mass spectrometry gives a direct proof of the presence of dimer and absence of higher aggregates. The restrained molecular dynamics simulations show the structural differences between drugs, which have been correlated to the biological action. A clear evidence of reduced cardiotoxicity by 4'-epiadriamycin, as compared to daunomycin and adriamycin, is demonstrated by mass spectrometry data.

journal_name

Eur J Med Chem

authors

Agrawal P,Barthwal SK,Barthwal R

doi

10.1016/j.ejmech.2008.09.037

subject

Has Abstract

pub_date

2009-04-01 00:00:00

pages

1437-51

issue

4

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(08)00459-5

journal_volume

44

pub_type

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