@article{ajps2018615,
author={{Y.M., Oyesakin and D.E., George and R.Y., Fadare and A.Y., Idris and O.A., Fadare},
title={Molecular Docking and <i>In-S</i><i>ilico</i> ADME Prediction of Substituted (<i>E</i>)-4-Styryl-7,8-dihydroquinazolin-5(6<i>H</i>)-ones and 5-((<i>E</i>)-Styryl)pyrimidine[4,5-d]pyrimidine-2,4(1<i>H</i>,3<i>H</i>)-diones as Potential SERT Inhibitors and Antidepressants},
journal={American Journal of Pharmacological Sciences},
volume={6},
number={1},
pages={25--32},
year={2018},
url={http://pubs.sciepub.com/ajps/6/1/5},
issn={2327-672X},
abstract={A set of 66 compounds from three classes having either of the two nuclei, (<i>E</i>)-4-styryl-7,8-dihydroquinazolin-5(6<i>H</i>)-one (<b>1</b>&#8242;<b>-22</b>&#8242;<b>a</b> and <b>1</b>&#8242;<b>-22</b>&#8242;<b>b</b>) and 5-((E)-styryl)pyrimido[4,5-d]pyrimidine-2,4(1<i>H</i>,3<i>H</i>)-dione (<b>1</b>&#8242;<b>-22</b>&#8242;<b>c</b>) were docked with Serotonin reuptake transporter (SERT) using escitalopram as the reference compound for comparison. Five of the compounds (<b>18</b>&#8242;<b>b</b>, <b>19</b>&#8242;<b>a</b>, <b>15</b>&#8242;<b>c</b>, <b>19</b>&#8242;<b>c</b> and <b>6</b>&#8242;<b>a)</b> had binding energy lower than/equal to that of escitalopram (-8.8 kcal/mol) and were eliminated from the study. The remaining 61 compounds were assessed for druglikeness using Lipinski¡¯s rule of five which led to the elimination of one more compound (<b>19</b>&#8242;<b>b)</b>. From among the remaining 60 compounds, 31 having binding energy equal to/greater than -10 kcal/mol were submitted for ADME properties prediction on an online program (preADMET) and the analysis of the results, taking into consideration the compounds blood brain barrier penetration and predicted P-glycoprotein inhibition as the major criteria for elimination, 11 compounds were selected for synthesis and further study as antidepressant agents. None of the 5-((E)-styryl)pyrimido[4,5-d]pyrimidine-2,4(1<i>H</i>,3<i>H</i>)-dione made it to the final eleven compounds due to high polarity that limits their BBB penetration. From among the 11 selected for synthesis are 3 compounds also that have very good hepatic metabolism (CYP450 enzymes interactions) pharmacokinetic profiles, predicted. The compounds selected for synthesis preferentially bind to the allosteric site of the SERT.},
doi={10.12691/ajps-6-1-5}
publisher={Science and Education Publishing}
}