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: In the drug discovery setting, undesirable ADMET properties of a pharmacophore with good predictive power obtained after a tedious drug discovery and development process may lead to late-stage attrition. The early-stage ADMET profiling has introduced a new dimension to leading development. Although several high-throughput in vitro models are available for ADMET profiling, however, the in silico methods are gaining more importance because of their economic and faster prediction ability without the requirements of tedious and expensive laboratory resources. Nonetheless, in silico ADMET tools alone are not accurate and, therefore, ideally adopted along with in vitro and or in vivo methods in order to enhance predictability power. This review summarizes the significance and challenges associated with the application of in silico tools as well as the possible scope of in vitro models for integration to improve the ADMET predictability power of these tools.

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RÉSUMÉ: La D-sérine en neurobiologie : neurotransmission et neuromodulation dans le SNC. l'homochiralité est fondamentale à la vie. Chez les organismes vivants, seuls les acides aminés lévogyres sont utilisés comme substrats pour la polymérisation et la formation de peptides et de protéines. Cependant, des acides aminés dextrogyres ont été détectés récemment dans différents organismes vivants dont des mammifères. parmi ces acides daminés, la d-sérine a été la plus étudiés. la d-sérine jouerait un rôle important comme neurotransmetteur dans le système nerveux central (SnC) chez l'humain en se liant au récepteur de la n-méthyl-d-aspartate (nMdar). la d-sérine se lie avec une haute affinité à un site co-agoniste du nMdar et, avec le glutamate, sert de médiateur dans plusieurs processus physiologiques et pathologiques vitaux dont la transmission nMdar, la plasticité synaptique et la neurotoxicité. C'est pourquoi on pense que la d-sérine jouerait un rôle clé comme déterminant de la neurotransmission médiée par nMdar dans le SnC des mammifères. dans ce contexte, nous revoyons les fonctions connues de la d-sérine en physiologie humaine, telles le développement du SnC et certaines pathologies comme les maladies neuropsychiatriques et neurodégénératives en lien avec une dysfonction de nMdar.

This version is available at https://strathprints.strath.ac.uk/7602/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the AbstractThe Lowry method and a capillary electrophoresis method were used to analyse protein residues in the supernatant after solvent deproteination of plasma. Acetonitrile and acetone were much more effective than methanol and ethanol at reducing the levels of proteins in plasma. The ability of different solvents to decrease levels of phospholipids in plasma samples was assessed using electrospray ionisation mass spectrometry (MS). Phospholipid signals can obscure differences between samples in general metabolite profiling (i.e. non-target compound) studies. Acetonitrile was much more effective than methanol in reducing the MS signal due to phospholipids in plasma which is a consequence of the poor solubility of phospholipids in acetonitrile. The capability of the solvents at reducing salts in urine samples was also studied by using an amperometric method. Using this approach little difference was detected between methanol, ethanol, acetonitrile and acetone in their ability to desalt urine samples.

α-3 carbonic anhydrase isozyme (CAIII) is the most abundant protein in adipocytes and considered insensitive to sulfonamide inhibitors. It was reported recently that the knock-down of CAIII is attributed with controlling lipogenesis. Thus inhibition of this target may lead to the discovery of new therapies against obesity and insulin resistance. Vanillic acid as a small molecule with coordinating groups and has a potential to bind zinc atoms in CA binding sites. Inhibition of CAIII by vanillic acid was evaluated by Hummel-Dreyer chromatography because it provides free interaction between ligand and macromolecule and introduces solution for faulty results obtained by current colorimetric assays. HPLC system of vanillic acid produces vacancy (negative) peak representing the amount of attached vanillic acid with CAIII. It was found that vanillic acid is able to bind with CAIII through two equilibria, one at equimolar ratio and another at 2:1 (vanillic acid-CAIII) ratio. The affinity constant of equimolar binding between CAIII and vanillic acid was found to be 14,400 m(-1) . It was found that vanillic acid binding with CAIII is much stronger than phenol and acetazolamide (positive controls).

The synthesis of new 7-(halophenylamino)-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid derivatives is described. Substitution of quinolonic compound 1a with chloro and fluoro aniline derivatives at position 7 produced target compounds 2-9 with relatively low yields. Alternatively, the product of correspondent carboxylate ester 1b subsequent with acid hydrolysis produced satisfactory yield. The prepared targets have shown interesting antibacterial properties against standard and resistant gram-positive strains. In particular, 2-chloro and 3-chloro aniline derivatives (3 and 4) depict MIC values of 6.7 and 0.9 lg/ml, respectively against standard S. aureous. Both compounds showed good activity against resistant strains of S. aureous.

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