Medicinal Chemistry

In the present investigation, in order to identify GI-safe anti-inflammatoryand analgesic agents, a series of novel 1, 2 and 5-substituted benzimidazole derivatives were synthesized and biologically evaluated. The results demonstrated that the compounds 3b, 4b, and 5b could serve as gastroprotective lead compounds for developing a novel class of potent as well as orally active anti-inflammatory and analgesic agents in the future research.

Cinnamoum reticulatum Hayata (Lauraceae) is an indigenous tree species in Taiwan. In this study, we further isolated the two flavonoids compounds kaempferol-3-O-(2",4"-di-E-p-coumaroyl)-α-L-rhamnopyranoside (1) and kaempferol-3-O-(3",4"-di-E-p-coumaroyl)-α-L-rhamnopyranoside (2) from the leaves and stems of C. reticulatum Hayate. The phytochemical characteristics, antioxidant and cytotoxic activities of the two compounds were evaluated. Kaempferol-3-O-(2",4"-di-E-p-coumaroyl)-α-L-rhamnopyranoside (1) and kaempferol-3-O-(3",4"-di-E-p-coumaroyl)-α- L-rhamnopyranoside (2) have antiproliferation activity in lung cancer cell line (A549 and NCI-H460) and breast cancer cell line (MCF-7 and MDA-MB-231). However, (1) displays better antioxidantactivity than (2). Our results showed that the two flavonoidsfrom C. reticulatum might have good potential for further development as chemoprevention or antioxidant remedies.

Recently, we have reported a series of 4-anilino-6,7-dimethoxyquinazolines as tyrosine kinase inhibitors with interesting in vitro IC50 values for the Epidermal Growth Factor Receptor (EGFR) and/or for the Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2). In this paper, we studied the impact of amino group in C-2 position of the quinazoline core on this series. The new synthesized compounds described herein were evaluated for both in vitro EGFR and VEGFR-2 kinase inhibition and antiproliferative activity in different cancer cell lines (PC3, HT29 and MCF7). 2-Aminoquinazolines substituted by a carbamic acid ester group present an interesting antiproliferative activity without tyrosine kinase inhibition. Thus, we drew the present study to explore the potential interaction of these molecules with the double-stranded DNA, the target of many conventional antitumor agents. We evaluated the strength and the way these molecules bind to DNA by UV-visible spectroscopy, circular dichroism, DNA thermal denaturation, and fluorescence measurements.

Inositol is a 6-carbon sugar alcohol that has been shown in limited studies to reduce retinopathy of prematurity and chronic lung disease in premature newborns. Developmentally it has a high concentration in the fetus that decreases with gestational age. It is transported from the fetus to the mother across the placenta. Although studies are underway to determine inositol kinetics in premature newborns treated therapeutically, the effects of gestational age, age after birth, and feeding on inositol concentrations after birth have not been studied adequately in premature newborns. Such studies would minimize blood removal and traumain preterm newborns by using plasma samples scavenged from the clinical laboratory to measure inositol after birth, if they remain stable. This report describes a new high pressure liquid chromatographic assay for inositol and its use to study the stability of inositol in conditions of storage that might be encountered within the clinical laboratory. The assay is linear from 0 to 1000 Μm with a lower limit of quantitation of 50 μM. Inositol in human plasma remains stable in refrigeration and at room temperature for up to 14 days and is not affected by storage in red blood cells that are intact or lysed. Anticoagulants encountered in clinical blood samples do not interfere with the chromatograms. Thus, it is feasible to measure the changes in inositol concentrations in plasma from preterm newborns that is scavenged from the clinical laboratory after storage for as long as 14 days.

Nanotechnologyis the study of extremely small structures, having size of 0.1 to 100 nm. Nano medicine is a relatively new field of science and technology. Brief explanation of various types of pharmaceutical nano systems is given. Classification of nano materials based on their dimensions is given. An application of Nanotechnology in various fields such as health and medicine, electronics, energy and environment, is discussed in detail. Applications of nano particles in drug delivery, protein and peptide delivery, cancer are explained. Applications of various nano systems in cancer therapy such as carbon nano tube, dendrimers, nano crystal, nano wire, nano shells etc. are given. The advancement in nano technology helps in the treatment of neuro degenerative disorders such as Parkinson’s disease and Alzheimer’s disease. Applications of nano technology in tuberculosis treatment, the clinical application of nanotechnology in operative dentistry, in ophthalmology, in surgery, visualization, tissue engineering, antibiotic resistance, immune response are discussed in this article. Nano pharmaceuticals can be used to detect diseases at much earlier stages.

Background: In this study, ultrasonic-microwave-assisted extraction (UMAE) was first applied to extract polysaccharides from the leaves of mulberry (PLM). The optimal conditions for polysaccharides extraction were determined by response surface methodology (RSM) along with central composite design (CCD) based on the singlefactor experiments. Extraction temperature (°C), extraction time (s), pH value, and ratio of water to raw material were investigated. Also, the antioxidant activities of PLM with UMAE were evaluated.

Results: According to statistical analysis, extraction temperature and pH value significantly affected extraction yield. The central composite design (CCD) showed that polynomial regression models were in good agreement with the experimental results with the coefficients of determination of 0.9263 for PLM. The optimal conditions were extraction temperature 76°C, extraction time 807 s, pH value 6.16 and the ratio of water to raw material 40:1, and the maximal yield of PLM was 10.29 ± 0.41(%). Meanwhile, DPPH radical-scavenging at EC50 values of PLM was found to be 128.3 μg/ml.

Conclusion: Under the optimal conditions, the experimental values agreed with value predicted by the model. The results suggested that UMAE could be used for the extraction of PLM, and the polysaccharides from mulberry leaves have significant antioxidant activities, which can be used as a source of potential antioxidant.

Chronickidney disease (CKD) is a significant and costly public health problem with increasing prevalence in most societies and the need for improved diagnosis. The aim of this study was to demonstrate how it is possible to decipher a combination of markers from a compendium of differentially-expressed proteins using available statistical tools when more than two study groups are involved. Screening for potential urinary biomarkerprofile stratifying early and later stages of CKD were performed. Sixteen patients with defined CKD staging were selected and compared with ten healthy individuals. Urinary proteins were quantified using theiTRAQ method and analysed with ProteinPilot, GenEx and Meta Core software. Four proteins (out of 194) (apolipoprotein D; protein AMBP; zinc-alpha-2-glycoprotein; and kininogen 1) were identified as critical for CKD stage separation. In conclusion, this preliminary work provides evidence that several unique urinary proteins are involved in early and later stages of CKD and suggests that a selected combination of biomarkers could be used to profile patients into different CKD stages. Further validation studies are now needed.

Objective To investigate the pharmacokinetics of cycloserine in healthy rat blood and lung tissues. Method Healthy rat blood and lung tissues were sampled in vivo by microdialysis sampling technique simultaneously. The concentrations of cycloserine in both blood and lung tissues were measured by high performance liquid chromatography mass spectrometry. All data were analyzed by Win Nonlin software. Results:The maximum concentration of free cycloserine in blood and lung tissue were (10.61 ± 2.42) mg/L and (1.53 ± 1.71) mg/L at 1h. And then both continued to decline. After administration the concentrations of free cycloserine in the blood has been higher than the concentrations in lung tissues. The area under the concentration curve (AUC) of free cycloserine was (33.53 ± 6.51) h·mg-1·L-1 in blood, and (4.49 ± 2.08) h·mg-1·L-1 in lung tissues.

Conclusion Microdialysis sampling technique combined with high performance liquid chromatography mass spectrometry / mass spectrometry can be accurately and objectively reflect the drug in the blood and tissues of the pharmacokinetic characteristics of cycloserine. Concentrations in lung tissues were significantly lower than concentrations in blood.

In this review, traditional Chinese medicine (TCM) history and importance were discussed. Tools and methods in the therapy were acknowledged. By TCM therapytreatment using herbal products, we can insert the energy into meridians and muscles which increase the person’s life force.