QSAR Studies of Uracil-Containing Histone Deacetylase Inhibitors

Abstract

Inhibitors of histone deacetylase (HDACs) are a new class of anticancer agents that affect gene regulation and have been shown to induce terminal differentiation of human tumor cell lines and to have antitumor effects in vivo. Quantitative structure activity relationship (QSAR) studies have been carried out in a series of new uracil based hydroxamide against maize HD2 inhibitory activities. The 2D QSAR studies activity is negatively influenced by the presence of electron donating substituent at the X-position whereas the contribution of hydrophobicity also shows negative effect. The best QSAR model with good correlation coefficient (r² = 0.775), of high statistical significance (> 99.9 %) well explained the variance in activity.