Predictability of Enantiomeric Chromatographic Behavior on Various Chiral Stationary Phases Using Typical Reversed Phase Modeling Software

Pharmaceutical companies worldwide tend to apply chiral chromatographic separation techniques in their mass production strategy rather than asymmetric synthesis. The present work aims to investigate the predictability of chromatographic behavior of enantiomers using DryLab HPLC method development software, which is typically used to predict the effect of changing various chromatographic parameters on resolution in the reversed phase mode. Three different types of chiral stationary phases were tested for predictability: macrocyclic antibiotics‐based columns (Chirobiotic V and T), polysaccharide‐based chiral column (Chiralpak AD‐RH), and protein‐based chiral column (Ultron ES‐OVM). Preliminary basic runs were implemented, then exported to DryLab after peak tracking was accomplished. Prediction of the effect of % organic mobile phase on separation was possible for separations on Chirobiotic V for several probes: racemic propranolol with 97.80% accuracy; mixture of racemates of propranolol and terbutaline sulphate, as well as, racemates of propranolol and salbutamol sulphate with average 90.46% accuracy for the effect of percent organic mobile phase and average 98.39% for the effect of pH; and racemic warfarin with 93.45% accuracy for the effect of percent organic mobile phase and average 99.64% for the effect of pH. It can be concluded that Chirobiotic V reversed phase retention mechanism follows the solvophobic theory. Chirality 25:506–513, 2013. © 2013 Wiley Periodicals, Inc.     

Thymoquinone causes multiple effects,including cell death,on dividing plant cells

Thymoquinone (TQ) is a major constituent of Nigella sativa oil with reported anti-oxidative activity and anti-inflammatory activity in animal cells. It also inhibits proliferation and induces programmed cell death (apoptosis) in human skin cancer cells. The present study sought to detect the influence of TQ on dividing cells of three plant systems and on expression of Bcl2-associated athanogene-like (BAG-like) genes that might be involved during the process of cell death. BAG genes are known for the regulation of diverse physiological processes in animals, including apoptosis, tumorigenesis, stress responses, and cell division. Synthetic TQ at 0.1 mg/mL greatly reduced wheat seed germination rate, whereas 0.2 mg/mL completely inhibited germination. An Evans blue assay revealed moderate cell death in the meristematic zone of Glycine max roots after 1 h of TQ treatment (0.2 mg/mL), with severe cell death occurring in this zone after 2 h of treatment. Light microscopy of TQ-treated (0.2 mg/mL) onion hairy root tips for 1 h revealed anti-mitotic activity and also cell death-associated changes, including nuclear membrane disruption and nuclear fragmentation. Transmission electron microscopy of TQ-treated cells (0.2 mg/mL) for 1 h revealed shrinkage of the plasma membrane, leakage of cell lysate, degradation of cell walls, enlargement of vacuoles and condensation of nuclei. Expression of one BAG-like gene, previously associated with cell death, was induced 20 min after TQ treatment in Glycine max root tip cells. Thus, TQ has multiple effects, including cell death, on dividing plant cells and plants may serve as a useful system to further investigate the mechanisms underlying the response of eukaryotic cells to TQ.     

Linagliptin,the dipeptidyl peptidase‐4 enzyme inhibitor,lessens CHOP and GRP78 biomarkers levels in cisplatin‐induced neurobehavioral deficits: A possible restorative gateway

Cisplatin (CP) is a cornerstone chemotherapeutic agent, however, its neurotoxicity is a chief cause of its limited usage. Linagliptin, which is a dipeptidyl peptidase‐4 enzyme inhibitor, has exhibited considerable neuroprotective potential. We aimed to evaluate the linagliptin modulatory effects on endoplasmic reticulum (ER) stress, redox status, and apoptosis in CP‐induced neurotoxicity. Thirty mice were allocated equally into the control group, Group II: CP group, and Group III: linagliptin treated CP group. All groups were subjected to the measurement of hippocampal messenger RNA gene expression of glucose‐regulated protein‐78 and C/EBP homologous protein (CHOP). Peroxisome proliferator‐activated receptor γ coactivator 1α and cleaved caspase‐3 levels were assessed by the enzyme‐linked immunosorbent assay technique while malondialdehyde, reduced glutathione levels and superoxide dismutase activity were detected spectrophotometrically. Linagliptin ameliorated ER stress and enhanced antioxidant status with cognitive function improvement. Linagliptin may be considered a promising neuroprotective agent owing to its ability to reduce ER/oxidative stress.     

Differential RNA-binding activity of the hnRNP G protein correlated with the sex genotype in the amphibian oocyte

A proteomic approach has enabled the identification of an orthologue of the splicing factor hnRNP G in the amphibians Xenopus tropicalis, Ambystoma mexicanum, Notophthalmus viridescens and Pleurodeles walt, which shows a specific RNA-binding affinity similar to that of the human hnRN G protein. Three isoforms of this protein with a differential binding affinity for a specific RNA probe were identified in the P. walt oocyte. In situ hybridization to lampbrush chromosomes of P. waltl revealed the presence of a family of hnRNP G genes, which were mapped on the Z and W chromosomes and one autosome. This indicates that the isoforms identified in this study are possibly encoded by a gene family linked to the evolution of sex chromosomes similarly to the hnRNP G/RBMX gene family in mammals.     

Synthesis,photophysical properties,anticancer evaluation,and molecular docking studies of new pyrimidine linked 4-arylidene-thiazolidin-4-ones as potent anticancer agents

The reaction of 4-(chloroacetamido)pyrimidine (1) with ammonium thiocyanate gave 2-(pyrimidin-4-ylimino)thiazolidin-4-one (2) , which, when condensed with four substituted benzaldehyde analogues, gave the consequent 5-arylidine-2-(pyrimidin-4-ylimino)thiazolidin-4-ones 3a–d . In addition, the absorbance and fluorescence behaviours of pyrimidinylimino-thiazolidin-4-one hybrids 3a–d in various organic solvents were investigated. The emphasis was on studying UV absorption capacities and the effect of various structural components on photophysical qualities such as the 5-arylidene-2-(pyrimidin-4-ylimino)thiazolidin-4-ones and N,N-dimethylamino tail. The cytotoxic effect of four pyrimidinylimino-thiazolidin-4-one hybrids 3a–d on tumour cell lines (HepG2, HCT-116, PC3, MCF-7) and a normal cell line (WI38) is investigated in this work. The cytotoxicity was measured by comparing the half-maximal inhibitory concentration (IC₅₀) to the reference medication, 5-fluorouracil. The findings indicate that these hybrid compounds had varying cytotoxic effects on the cell lines examined; hybrids 3b and 3c demonstrated significant anticancer activity against MCF-7 with IC₅₀ values of 7.53 ± 0.43 and 9.17 ± 0.31 μM, respectively. The inhibitory efficacy of various synthesized hybrids on the epidermal growth factor receptor (EGFR) kinase was investigated. EGFR is a crucial target in cancer treatment because inhibiting it may reduce tumour development and proliferation. The IC₅₀ value was used to calculate the inhibitory activity, which is the concentration of inhibitor necessary to induce half-maximal inhibition of EGFR kinase activity. In addition, the predicted ADME results show that pyrimidinylimino-thiazolidin-4-one hybrids have good pharmacokinetic properties; hybrid 3d is more lipophilic than the other compounds. It has a medium molecular weight, a small number of hydrogen bond acceptors and donors, and a large number of aromatic heavy atoms. Moreover, molecular docking simulations revealed precise information on the interactions of pyrimidinylimino-thiazolidin-4-one hybrids 3a–d and 5-Fu with their respective protein targets. These interactions point to possible pathways for their biological activities and call for more testing to establish their effectiveness as bioactive molecules or therapeutic candidates.     

Motifs in the assembly of food web networks

The assembly of local communities from regional pools is a multifaceted process that involves the confluence of interactions and environmental conditions at the local scale and biogeographic and evolutionary history at the regional scale. Understanding the relative influence of these factors on community structure has remained a challenge and mechanisms driving community assembly are often inferred from patterns of taxonomic, functional, and phylogenetic diversity. Moreover, community assembly is often viewed through the lens of competition and rarely includes trophic interactions or entire food webs. Here, we use motifs – subgraphs of nodes (e.g. species) and links (e.g. predation) whose abundance within a network deviates significantly as compared to a random network topology – to explore the assembly of food web networks found in the leaves of the northern pitcher plant Sarracenia purpurea. We compared counts of three‐node motifs across a hierarchy of scales to a suite of null models to determine if motifs are over‐, under‐, or randomly represented. We then assessed if the pattern of representation of a motif in a given network matched that of the network it was assembled from. We found that motif representation in over 70% of site networks matched the continental network they were assembled from and over 75% of local networks matched the site networks they were assembled from for the majority of null models. This suggests that the same processes are shaping networks across scales. To generalize our results and effectively use a motif perspective to study community assembly, a theoretical framework detailing potential mechanisms for all possible combinations of motif representation is necessary.     

Microstructure of scales in selected lizard species

In the present study, it was hypothesized that micromorphology of the surface of many lizard scales appears to mimic the topography of the habitat in which they live. Many authors have suggested that the microstructure of the superficial surface of scales have undergone important adaptations and have functional value in lizards. In this study, we investigated the variation and adaptation of the micromorphology and microstructure of the superficial surface of the dorsal and ventral scales from the mid-body region of Stellagama stellio (Agamidae), Stenodactylus petrii (Gekkonidae), Acanthodactylus boskianus (Lacertidae), Eumeces schneideri (Scincidae), Trachylepis quinquetaeniata (Scincidae), Scincus scincus (Scincidae), Varanus griseus (Varanidae), Chameleo chameleon (Chamaeleonidae). Skin specimens were prepared and analyzed using scanning electron microscopy. The dorsal and ventral scale surfaces had microstructure in the studied species and they exhibited unique patterns that somewhat resembled the topography of the microhabitats in which they lived. Similarity was detected in the three most related species, those having a common family, Scincidae. Ecomorphological relationships were detected between the dorsal and ventral scale microstructures and microhabitats. We conclude that environmental factors have observable influences on the microstructure of lizard scales.