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J Mol Graph Model. 2016 Sep;69:39-60. doi: 10.1016/j.jmgm.2016.07.010. Epub 2016 Aug 18.

The molecular shape and the field similarities as criteria to interpret SAR studies for fragment-based design of platinum(IV) anticancer agents. Correlation of physicochemical properties with cytotoxicity.

Author information

1
Instituto de Biotecnología y Biomedicina Vicent Villar Palasí, Universidad Autónoma de Barcelona, Bellaterra, 08193 Barcelona, Spain.
2
Unidad de Química Orgánica Industrial y Aplicada, Departamento de Química Orgánica, Universidad de Barcelona, Martí i Franquès 1-11, 08028 Barcelona, Spain. Electronic address: angel.montana@ub.edu.

Abstract

Molecular shape similarity and field similarity have been used to interpret, in a qualitative way, the structure-activity relationships in a selected series of platinum(IV) complexes with anticancer activity. MM and QM calculations have been used to estimate the electron density, electrostatic potential maps, partial charges, dipolar moments and other parameters to correlate the stereo-electronic properties with the differential biological activity of complexes. Extended Electron Distribution (XED) field similarity has been also evaluated for the free 1,4-diamino carrier ligands, in a fragment-based drug design approach, comparing Connolly solvent excluded surface, hydrophobicity field surface, Van der Waals field surface, nucleophilicity field surface, electrophilicity field surface and the extended electron-distribution maxima field points. A consistency has been found when comparing the stereo-electronic properties of the studied series of platinum(IV) complexes and/or the free ligands evaluated and their in vitro anticancer activity.

KEYWORDS:

Anticancer agents; Cytotoxicity; Drug likeness; Platinum-based drugs; Shape and field similarity; Stereo-electronic effects; Structure-activity relationship; Structure-related molecular properties; XED field

PMID:
27567201
DOI:
10.1016/j.jmgm.2016.07.010
[Indexed for MEDLINE]

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