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Histone deacetylase inhibitors (HDACIs). Structure—activity relationships: history and new QSAR perspectives
Author(s) -
Pontiki Eleni,
HadjipavlouLitina Dimitra
Publication year - 2012
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.20200
Subject(s) - quantitative structure–activity relationship , molar refractivity , histone deacetylase , steric effects , chemistry , lipophilicity , stereochemistry , pharmacology , biochemistry , histone , biology , gene
Histone deacetylase (HDAC) inhibition is a recent, clinically validated therapeutic strategy for cancer treatment. HDAC inhibitors (HDACIs) block angiogenesis, arrest cell growth, and lead to differentiation and apoptosis in tumor cells. In this article, a survey of published quantitative structure–activity relationships (QSARs) studies are presented and discussed in the hope of identifying the structural determinants for anticancer activity. Secondly a two‐dimensional QSAR study was carried out on biological results derived from various types of HDACIs and from different assays using the C‐QSAR program of Biobyte. The QSAR analysis presented here is an attempt to organize the knowledge on the HDACIs with the purpose of designing new chemical entities with enhanced inhibitory potencies and to study the mechanism of action of the compounds. This study revealed that lipophilicity is one of the most important determinants of activity. Additionally, steric factors such as the overall molar refractivity (CMR), molar volume (MgVol), the substituent's molar refractivity (MR) (linear or parabola), or the sterimol parameters B 1 and L are important. Electronic parameters indicated as σ p , are found to be present only in one case. © 2010 Wiley Periodicals, Inc. Med Res Rev 32:1‐165, 2012