Body weight gain for mice fed HFD diet and control chow over 8 weeks.

<p>**** p < 0.0001.</p

Stability values for targeted TCA intermediates under different conditions.

<p>Stability values for targeted TCA intermediates under different conditions.</p

Representation of the TCA cycle and anaplerotic energy metabolites, showing metabolite levels after HFD (H) and control chow (C) feeding to 8 week-old mice for 8 weeks.

<p>Ordinate axes represent metabolite peak area/IS peak area, except for SLC5A6 expression (top right), where the ordinate represents mRNA expression.</p

Changes for the serum energy metabolite/IS ratios for HFD (H)- and control chow diet (C)-fed mice (n = 5).

<p>A, pyruvic acid; B, citric acid; C, <i>cis</i>-aconitic acid; D, succinic acid; E, fumaric acid; F, malic acid; G, 2-oxoglutaric acid; H, glutamine; I, glutamic acid; J, lactic acid; K, isocitric acid; L, pantothenic acid. *p<0.05; **p<0.01.</p

The results of targeted TCA intermediates in serum and liver.

<p>The results of targeted TCA intermediates in serum and liver.</p

Intra- and inter-day precision and accuracy of quality control samples for targeted TCA metabolites.

<p>Intra- and inter-day precision and accuracy of quality control samples for targeted TCA metabolites.</p

Quantitation by GCMS of energy metabolites.

<p>Quantitation by GCMS of energy metabolites.</p

Representative single ion monitoring chromatograms of the energy metabolites.

<p>a) pyruvic acid, b) succinic acid, c) fumaric acid, d) malic acid, e) oxaloacetic acid, f) 2-oxoglutaric acid, g) <i>cis</i>-aconitic acid, h) citric acid, i) DL-norleucine (IS), j) lactic acid, k) glutamine, l) glutamic acid, m) isocitrate, and n) pantothenic acid at MQC (20.0 μM).</p

Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer’s disease

<p>Alzheimer’s disease (AD) is one of the most significant neurodegenerative disorders and its symptoms mostly appear in aged people. Catechol-o-methyltransferase (COMT) is one of the known target enzymes responsible for AD. With the use of 23 known inhibitors of COMT, a query has been generated and validated by screening against the database of 1500 decoys to obtain the GH score and enrichment value. The crucial features of the known inhibitors were evaluated by the online ZINC Pharmer to identify new leads from a ZINC database. Five hundred hits were retrieved from ZINC Pharmer and by ADMET (absorption, distribution, metabolism, excretion, and toxicity) filtering by using FAF-Drug-3 and 36 molecules were considered for molecular docking. From the COMT inhibitors, opicapone, fenoldopam, and quercetin were selected, while ZINC63625100_413 ZINC39411941_412, ZINC63234426_254, ZINC63637968_451, and ZINC64019452_303 were chosen for the molecular dynamics simulation analysis having high binding affinity and structural recognition. This study identified the potential COMT inhibitors through pharmacophore-based inhibitor screening leading to a more complete understanding of molecular-level interactions.</p