Inhibition values of 4, 10, 13 and 14 against the catalytic domain of hDNMT3A, hDNMT1 and G9a.

<p>^*Values are means of at least three experiments. ^†Compounds were tested in a 10-dose IC₅₀ mode with 2-fold serial dilution starting at 400 µM. For <b>4</b>, <b>13</b> and <b>14</b> it was no possible to determine IC₅₀ values (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096941#pone.0096941.s001" target="_blank">File S1</a>).</p

Docking studies of 4 and 14 into the DNMT3A active site.

<p>Experimental (A) and theoretical (B and C) binding mode of AdoHcy (A), <b>4</b> (B) and <b>14</b> (C) in the DNMT3A active site. Protein is depicted as light yellow ribbons and sticks while ligands are depicted as red sticks. Hydrogen-bonds are depicted as dashed blue lines.</p

Quinazoline-based modulators of epigenetic targets.

<p>(A) Known quinazolines (<b>1–3</b>) as G9a/GLP inhibitors. (B) Novel 6,7-desmethoxyquinazolines <b>4–18</b>. (C) Synthetic scheme for the preparation of <b>4–18</b>.</p

Effects of selected compounds in human lymphoma U-937 and RAJI cells.

<p>Cells were treated with the indicated concentration of compounds <b>4</b>, <b>10</b>, <b>13</b> and <b>14</b> for up to 72 h. Antiproliferative effects (left) and cell death induction (right) on (A) U-937 and (B) RAJI lymphoma cell lines. Results are the mean ± SD of at least three independent experiments. *, **, *** indicate p<0.05, p<0.01, p<0.005 versus untreated cells, respectively.</p

Effect of selected quinazoline analogues <b>4</b>, <b>10</b>, <b>13</b> and <b>14</b> on human lymphoma U-937 and RAJI cell viability at 48 h^*.

<p>*Data represent the mean (± SD) of at least three independent experiments.</p

Percent of inhibition of <b>4–18</b> against hDNMT1 and hDNMT3A.

<p>Values are means of two to five experiments ± standard deviation.</p>†<p>ND, not determined.</p><p>*Percent of inhibition at 32 and 10 µM: 18±0.8 and 6.5±0.7%, respectively.</p