Combinatorial Chemistry & High Throughput Screening - Volume 16, Issue 7, 2013

The aim of this study is (i) to prepare estrone-imprinted nanospheres (nano-EST-MIPs) and (ii) to integrate them into the electrochemical sensor as a recognition layer. N-methacryloyl-(l)-phenylalanine (MAPA) was chosen as the complexing monomer. Firstly, estrone (EST) was complexed with MAPA and the EST-imprinted poly(2-hyroxyethylmethacrylate-co-N-methacryloyl-(l)-phenylalanine) [EST-imprinted poly(HEMA–MAPA)] nanospheres were synthesized by surfactant- free emulsion polymerization method. The specific surface area of the EST-imprinted poly(HEMA–MAPA) nanospheres was found to be 1275 m2/g with a size of 163.2 nm in diameter. According to the elemental analysis results, the nanospheres contained 95.3 mmole MAPA/g nanosphere. The application of EST specific MIP nanospheres for the development of an electrochemical biosensor was introduced for the first time in our study by using electrochemical impedance spectroscopy (EIS) technique. This nano-MIP based sensor presented a great specificity and selectivity for EST.

Bioassay record of High Throughput Screening (HTS) contains compounds with high diversity. This high diversity in molecules causes an intense non-linearity into the molecular descriptors set. So to build a QSAR model covering the diversity in molecular structure is a tedious task. In the present work, a method has been proposed to extract information about pharmacophores covering a larger area in the HTS record and development of Support Vector Regression (SVR) QSAR model considering extracted pharmacophores specified to the cell line or target. A probabilistic approach has also been proposed to evaluate the authenticity of predictions made by QSAR model. The developed method has been used for virtual screening of library molecules. The advantage of this protocol is that, it is beneficial for a very large dataset. The proposed method has the capability to extract pharmacophore information from any HTS data. Additionally, this will be advantageous for the development of precised virtual screening model on the basis of high throughput screening data.

G protein-coupled receptors (GPCRs) are signaling molecules with a wide variety of skills. Members of this large family of membrane protein have been shown to regulate the activities of the different signaling pathways of the ligand specific manner. α2–adrenoceptors (α2-ARs) are one of the GPCRs and the stimulation of them could modulate many classical effects such as hypotension, bradycardia, etc.. Recently, α2A-AR is more and more important for its role in the therapeutic applications in central nervous system (CNS) diseases. High throughput screening of α2A-AR agonists was established by LANCETM cAMP assay from a compound library of 80,000 small-molecule compounds to find out potential human α2A-adrenoceptor (α2A-AR) agonists that might have therapeutic effect in CNS diseases. From the preliminary and secondary screening, 37 compounds were identified as α2AAR agonists, and six compounds among them presented more pronounced α2A-AR stimulating activity than guanfacine, a selective α2A-AR agonist. The study provided referred data for the development of potent α2A-AR agonists and suggested that the existence of the parent structure (1, 2, 4-benzothiadiazine 1, 1-dioxide) bodes well for pharmaceutical development of α2A-AR agonists.

TLC bioautography is a method that combines chromatographic separation and in situ biological activity determination. The antimicrobial, antioxidant and enzyme inhibitory activities can be performed on TLC bioautography. This method is mainly used for preliminary screening natural products possessing these biological activities and for the bioactivity-directed fractionation and isolation of active components from complex extracts. This review covers the mechanisms and methodology of the antimicrobial, antioxidant activities, and enzyme inhibition adopted on TLC. It will be in particular discuss the recent advances in these technologies and assess their applications in targeting natural products.

Three-component reaction of aldehyde, 1H-indazol-6-amine and 1,3-dicarbonyl compounds in EtOH under catalyst-free conditions, generates the corresponding pyrazolo[3,4-a]acridine, cyclopenta[b]pyrazolo[3,4-f]quinoline, indeno[1,2-b]pyrazolo[3,4-f]quinoline and benzo[h]pyrazolo[3,4-a]acridine derivatives in high yields and regioselectivity, respectively. The dicarbonyl compounds include 5,5-dimethylcyclohexane-1,3-dione, cyclopentane-1,3-dione, 2H-indene- 1,3-dione and 2-hydroxynaphthalene-1,4-dione.

A library of supramolecular structures formed by self-organization of N-lipidated tripeptides, dipeptides and Nacylated amino acids attached to cellulose according to the TASP concept via aminophenylamino-1,3,5-triazine was synthesized and the catalytic activity of the structures was studied. Intensive catalytic activity in solvolysis of sterically hindered Z-Aib-Aib-ONp under ambient conditions was observed for structures bearing the catalytic triad as well as for structures with the peptide fragment shortened to a dipeptide or even a single Ser, Glu or His residue, but not for structures bearing alanine or phenylalanine residues. For all structures with a dipeptide or a single amino acid residue and for most of tripeptide structures the progress of solvolysis was stopped after the concentration of the nitrophenolate ion reached 0.5–0.7 x 10-4 M/L. Only in the case of catalysts with glutamic acid residues in the tripeptide fragment, solvolysis proceeded until all the substrate was consumed.

Four fluorescent tricyclic basic dyes with two hollow organic capsules namely cucurbit[n]urils (CB[n]), n = 7 and 8, compose the chemical tongue that is examined for α-amino acids recognition. This array is able to identify and discriminate 18 α-amino acids up to 10-4 M without the need of enzyme activation. The paper shows the importance of the classification technique employed in order to reach the highest recognition rate at this concentration.