Synthesis of new sulfonamide inhibitors of carbonic anhydrase

Four different derivatives of aromatic sulfonamides have been synthesized: 1,2-bis[(4-sulfonamidobenzamide)ethoxy]ethane (SBAM), 1,2-bis[(4-sulfonamidobenzoate)ethoxy]ethane, 1,2-bis[(2,4-dichloro-5-sulfonamidobenzamide)ethoxy]ethane, and 1,2-bis[(2,4-dichloro-5-sulfonamidobenzoate)ethoxy]ethane. SBAM is a most potent inhibitor on ciliary epithelium carbonic anhydrase and is approximately 13 times more active against carbonic anhydrase isoform II than against isoform I.     

Antimicrobial and biological effects of ipemphos and amphos on bacterial and yeast strains

In this study, the antimicrobial effects of monophosphazenes such as SM ipemphos and amphos were examined on bacterial and yeast strains. In addition, the biological effects of these compounds were tested on the lipid level of Saccharomyces cerevisiae and Candida albicans cells. The SM has an antimicrobial effect on the bacterial and yeast strains within the range of 100 and 1500 microg. When the concentration was increased, the inhibition zone expanded on the growth media ( p < 0.01; p < 0.001). The ipemphos did not affect the bacterial and yeast cells in the 100 and 600 microg range. In addition, the amphos did not show an antimicrobial effect on the bacterial cells between 100 and 300 microg or on yeast cells at any of the administered concentrations. In vitro media, the biological effects of these molecules were compared with vitamin E, melatonin and fish oil on the yeast cells. We have found that monophosphazenes have growth effects on the cells in vitro media. The lipid level of S. cerevisiae cells was decreased by 300 microg doses of vitamin E, fish oil, and ipemphos (respectively; p < 0.05, p < 0.01, and p < 0. 001). In addition, the lipid levels of the same yeast cells were depressed by 1000-microg doses in all supplemented groups. However, it was observed that the highest decrease in lipid level of S. cerevisiae cells occurred in the amphos group ( p < 0.001). The lipid levels of the C. albicans cells were significantly reduced ( p < 0.01) by 300 microg of amphos and melatonin. In contrast, the vitamin E and fish oil significantly raised ( p < 0.01; p < 0.001) the lipid level of the same yeast cell, as compared with the control. In addition, the lipid level of these cells was increased by administration of 1000 microg vitamin E, and melatonin ( p < 0.01). In conclusion, while high concentrations of ipemphos and amphos have an antimicrobial effect on bacterial and yeast cells, amphos did not affect the yeast cells. While ipemphos and amphos increased cell growth in media, they reduced the lipid level of C. albicans and S. cerevisiae. In addition, the antioxidants such as vitamin E, melatonin, and fish oils affected the lipid level of yeast cells.     

Diverse effects of three furocoumarins on human lymphocyte proliferation

The biological effects of three furocoumarins on the proliferation of human normal peripheral blood lymphocytes have been investigated. Mitogen-stimulated human lymphocytes were assayed "in vitro" by measuring 3H-thymidine (3H-TdR) incorporation in the presence and in the absence of 15-30 microM 3-carbethoxypsoralen (3-CPs), trimethylangelicin (TMA) and psoralen (PSR) with and without UV-A irradiation (365 nm). The three furocoumarins differ in their ability to form mono- and bi-functional adducts with DNA pyrimidine bases and in producing reactive species of oxygen. At low furocoumarin doses and short times of UV-A irradiation (15-30 sec) used in the present study, 3-CPs did not affect 3H-TdR incorporation in PHA-stimulated human lymphocytes, TMA strongly inhibited 3H-TdR incorporation, while, unexpectedly, PSR increased 3H-TdR incorporation in the absence of irradiation, likely acting, under these experimental conditions, as a co-mitogen.     

Antifungal activity of essential oils against three vegetative-compatibility groups of <Emphasis Type="Italic">Verticillium dahliae</Emphasis>

The antifungal activities of volatile phase effects of essential oils from Origanum onites, O. syriacum, O. minutiflorum, O. vulgare, O, marjorana, Thymus vulgaris, T. serpyllum, Rosmarinus officinalis, Salvia officinalis and Micromeria fruticosa were evaluated for their ability to inhibit growth of three vegetative compatibility groups (VCGs) of Verticillium dahliae. Carvacrol was the main component of O. onites, O. minutiflorum and O. vulgare essential oils, while γ-terpinene was the main component of O. syriacum. P-cymene and thymol were the dominant component of T. vulgaris and T. serpyllum. β- thujone and l-camphor were the main component of S. officinalis. Polegone and isomenthone were the dominant components of M. fruticosa essential oil. Based on the in vitro test, the degree of fungistatical effects can be ranked in the following order of inhibition: O. syriacum = O. onites = O. minutiflorum = O. vulgare = T. vulgaris > T. serpyllum > M. fruticosa > S. officinalis = O. marjorana > R. officinalis. The essential oils of S. officinalis, O. marjorana and R. officinalis displayed moderate antifungal activity, that increased with increasing concentrations. Among the VCGs, VCG2A and VCG4B were found to be highly sensitive to the essential oils. The essential oils of O. syriacum, O. onites, O. minutiflorum, O. vulgare and T. vulgaris were the most efficacious, demonstrating strong antifungal activity against all of the tested VCGs of V. dahliae at relatively low concentrations and they could find practical application as natural fungicides in the prevention and protection of plants from V. dahliae infections.     

Differential protein input in the maternal diet alters the skeletal muscle transcriptome in fetal sheep

Mammalian Genome - Maternal nutrition during pregnancy is one of the major intrauterine environmental factors that influence fetal development by significantly altering the expression of genes that...     

Tandem mass spectrometry approach for the investigation of the steroidal metabolism: Structure–fragmentation relationship (SFR) in anabolic steroids and their metabolites by ESI-MS/MS analysis

Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to investigate the effect of different substitutions introduced during metabolism on fragmentation patterns of four anabolic steroids including methyltestosterone, methandrostenolone, cis-androsterone and adrenosterone, along with their metabolites. Collision-induced dissociation (CID) analysis was performed to correlate the major product ions of 19 steroids with structural features. The analysis is done to portray metabolic alteration, such as incorporation or reduction of double bonds, hydroxylations, and/or oxidation of hydroxyl moieties to keto functional group on steroidal skeleton which leads to drastically changed product ion spectra from the respective classes of steroids, therefore, making them difficult to identify. The comparative ESI-MS/MS study also revealed some characteristic peaks to differentiate different steroidal metabolites and can be useful for the unambiguous identification of anabolic steroids in biological fluid. Moreover, LC–ESI-MS/MS analysis of fermented extract of methyltestosterone, obtained by Macrophomina phaseolina was also investigated.     

Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury

Human ESC-derived mesenchymal stem cell (MSC)-conditioned medium (CM) was previously shown to mediate cardioprotection during myocardial ischemia/reperfusion injury through large complexes of 50–100 nm. Here we show that these MSCs secreted 50- to 100-nm particles. These particles could be visualized by electron microscopy and were shown to be phospholipid vesicles consisting of cholesterol, sphingomyelin, and phosphatidylcholine. They contained coimmunoprecipitating exosome-associated proteins, e.g., CD81, CD9, and Alix. These particles were purified as a homogeneous population of particles with a hydrodynamic radius of 55–65 nm by size-exclusion fractionation on a HPLC. Together these observations indicated that these particles are exosomes. These purified exosomes reduced infarct size in a mouse model of myocardial ischemia/reperfusion injury. Therefore, MSC mediated its cardioprotective paracrine effect by secreting exosomes. This novel role of exosomes highlights a new perspective into intercellular mediation of tissue injury and repair, and engenders novel approaches to the development of biologics for tissue repair.     

β‐Hydroxyamide‐Based Ligands and Their Use in the Enantioselective Borane Reduction of Prochiral Ketones

Hydroxyamide‐based ligands have occupied a considerable place in asymmetric synthesis. Here we report the synthesis of seven β‐hydroxyamide‐based ligands from the reaction of 2‐hydroxynicotinic acid with chiral amino alcohols and test their effect on the enantioselective reduction of aromatic prochiral ketones with borane in tetrahydofuran (THF). They produce the corresponding secondary alcohols with up to 76% enantiomeric excess (ee) and good to excellent yields (86‐99%). Chirality 26:21–26, 2013. © 2013 Wiley Periodicals, Inc.