The identification of novel PLC-γ inhibitors using virtual high throughput screening

New inhibitors of tyrosyl-DNA phosphodiesterase I (Tdp 1) combining 7-hydroxycoumarin and monoterpenoid moieties

“…29 The screening approach used has been previously successfully applied to find active ligands against the Phosphoinositide specificphospholipase C-γ2 enzyme and Autophagy. 30,31 A detailed description of the virtual screen is given in the Methodology section. Sixteen compounds were selected for experimental testing and compound 6, which is 3-methoxybenzyl derivative of 7-hydroxycoumarin annelated with the cyclohexane ring (Scheme 1), was identified as a promising inhibitor with an IC 50 value of 5 μM using our oligonucleotide-based fluorescence assay.…”

Glycophenotype of breast and prostate cancer stem cells treated with thieno[2,3-<em>b</em>]pyridine anticancer compound

“…The molecular structure of compound 1 used in this study is shown in Figure 1. The efficacy of the thieno[2,3- b ]pyridines was discovered by virtual high-throughput screen (vHTS) against the phospholipase C-γ2 (PLC-γ2) isoform 20. The administration of thieno[2,3- b ] pyridines causes the breast cancer cell line MDA-MB-231 to be severely growth restricted, rounded and blebbing of the plasma membrane, G 2 /M phase population increase in the cell cycle and decrease in motility as reflected in slowed proliferation in scratch assays 21.…”

Temperature‐Controlled Base‐Promoted Cyclization for the Synthesis of 2‐Amino‐4H‐benzo[d][1,3]thiazin‐4‐ones and 2‐Thioxo‐4(3H)‐quinazolinones

“…In particular, 2‐thioxo‐2,3‐dihydroquinazolin‐4(1 H )‐ones are versatile building blocks with a cyclic thiourea moiety used commonly as intermediates toward various quinazolinone‐containing molecules, including fluquinconazole . Moreover, 2‐amino‐4 H ‐benzo[ d ][1,3]thiazin‐4‐ones are valuable small molecules that have been shown to inhibit complement C1r protease, phospholipase C‐γ, monoamine oxidase B (MAO‐B) and the adenosine receptors (AR) . Recently, Heinemann and Kostenis reported that Gue1157 and Gue1158 served as potential G protein‐coupled receptor antagonists (GPCR) with a notable disparity of efficacy for Gα i ‐mediated versus Gβγ‐mediated cellular events …”