Direct Introduction of an Alkylsulfonamido Group on C-sites of Isomeric Dicarba-closo-dodecaboranes: The Influence of Stereochemistry on Inhibitory Activity against the Cancer-Associated Carbonic Anhydrase IX Isoenzyme

Carbonic anhydrase IX (CA IX), a tumor-associated metalloenzyme, represents a validated target for cancer therapy and diagnostics. Herein, we report the inhibition properties of isomeric families of sulfonamidopropyl-dicarba-closo-dodecaboranes group(s) prepared using a new direct five-step synthesis from the corresponding parent cages. The protocol offers a reliable solution for synthesis of singly and doubly substituted dicarba-closo-dodecaboranes with a different geometric position of carbon atoms. The closo-compounds from the ortho- and meta-series were then degraded to corresponding 11-vertex dicarba-nido-undecaborate(1−) anions. All compounds show in vitro enzymatic activity against CA IX in the low nanomolar or subnanomolar range. This is accompanied by clear isomer dependence of the inhibition constant (K_i) and selectivity towards CA IX. Decreasing trends in K_i and selectivity index (S_I) values are observed with increasing separation of the cage carbon atoms. Interactions of compounds with the active sites of CA IX were explored with X-ray crystallography, and eight high-resolution crystal structures uncovered the structural basis of inhibition potency and selectivity.     

Synthesis of 5-oxo-5H-chromeno[3,4-c]pyridine-1-carbonitriles and features of their NMR spectra

Two different methods leading to 5-oxo-5H-chromeno[3,4-c]pyridine-1-carbonitriles were investigated. Reactions of 3-aminocrotonirile with substituted salicylaldehydes provided 5-oxo-5H-chromeno[3,4-c]pyridine-1-carbonitriles with the same substituent on positions 2 and 4 of the system. The reaction of 3-aminocrotonirile with variety of substituted 3-acetylcoumarins lead to 5-oxo-5H-chromeno[3,4-c]pyridine-1-carbonitriles with different substituents on positions 2 and 4. The structures of the products were confirmed by spectroscopic methods. The presence of nitrile moiety in the structures with fixed geometry caused the highly downfield shift of the aromatic proton at position 10 in ¹H NMR spectrum. The electronic factor of the substituents caused variation of this downfield shift.     

Solvent Mixture Optimization in the Extraction of Bioactive Compounds and Antioxidant Activities from Garlic (Allium sativum L.)

Garlic is a health promoter that has important bioactive compounds. The bioactive extraction is an important step in the analysis of constituents present in plant preparations. The purpose of this study is to optimize the extraction with the best proportion of solvents to obtain total phenolic compounds (TPC) and thiosulfinates (TS) from dried garlic powder, and evaluate the antioxidant activities of the optimized extracts. A statistical mixture simplex axial design was used to evaluate the effect of solvents (water, ethanol, and acetone), as well as mixtures of these solvents, after two ultrasound extraction cycles of 15 min. Results showed that solvent mixtures with a high portion of water and pure water were efficient for TPC and TS recovery through this extraction procedure. According to the regression model computed, the most significant solvent mixtures to obtain high TPC and TS recovery from dried garlic powder are, respectively, the binary mixture with 75% water and 25% acetone and pure water. These optimized extracts presented oxygen radical absorbance capacity. Pure water was better for total antioxidant capacity, and the binary mixture of water–acetone (75:25) was better for DPPH scavenging activity. These optimized extracts can be used for industrial and research applications.     

Ionization effects and linear stability in a coaxial plasma device

A 2-D computer simulation of a coaxial plasma device depending on the conservation equations of electrons, ions and excited atoms together with the Poisson equation for a plasma gun is carried out. Some characteristics of the plasma focus device (PF) such as critical wave numbers a _c and voltages U _c in the cases of various pressures Pare estimated in order to satisfy the necessary conditions of traveling particle densities (i.e. plasma patterns) via a linear analysis. Oscillatory solutions are characterized by a nonzero imaginary part of the growth rate (σ) for all cases. The model also predicts the minimal voltage ranges of the system for certain pressure intervals.      

A comparative study on various spectrometries with thin layer chromatography for simultaneous analysis of drotaverine and nifuroxazide in capsules

Three spectrophotometric methods including Vierordt's method, derivative, ratio spectra derivative, and thin layer chromatography (TLC)-UV densitometric method were developed for simultaneous determination of drotaverine HCl (DRT) and nifuroxazide (NIF) in presence of its impurity, 4-hydroxybenzohydrazide (4-HBH). In Vierordt's method, (E(1 cm)(1%)) values were calculated at 227 and 368 nm in the zero-order spectra of DRT and NIF. By derivative spectrophotometry, the zero-crossing method, drotaverine HCl was determined using the second derivative at 245 nm and the third derivative at 238 nm, while nifuroxazide was determined using the first derivative at 399 nm and the second derivative at 411 nm. The ratio spectra derivative spectrophotometry is basedon the measure of the amplitude at 459 nm for DRT and at 416 nm for NIF in the first derivative of the ratio spectra. Calibration graphs of the three spectrophotometric methods were plotted in the range 1-10 mug/ml of DRT and 2-20 mug/ml of NIF. TLC-UV densitometric method was achieved on silica gel plates using ethyl acetate : methanol : ammonia 33% (10 : 1 : 0.1 v/v/v) as the mobile phase. The Rf values were 0.74, 0.50, 0.30+/-0.01 for DRT, NIF and 4-HBH, respectively. On the fluorescent plates, the spots were located by fluorescence quenching and the densitometrical area were measured at 308 and 287 nm with linear range 0.2-4 mug/spot and 0.6-12 mug/spot for DRT and NIF, respectively. The proposed methods have been successfully applied to the commercial pharmaceutical formulation without any interference of excipients. Mean recoveries, relative standard deviations and the results of the proposed methods were compared with those obtained by applying the alternate methods.     

Myrothecoside,a Novel Glycosylated Polyketide from the Terrestrial Fungus Myrothecium sp. GS‐17

Based on the chemical analysis and targeted bioactivity screening, a new polyketide glycoside, myrothecoside, was isolated from a terrestrial halotolerant fungus, Myrothecium sp. GS‐17. The structure of myrothecoside was elucidated on the basis of extensive spectroscopic analysis including 1D‐ and 2D‐NMR (¹H,¹H‐COSY, HSQC, HMBC, and NOESY) experiments, combined with mass spectroscopic data and physicochemical properties. This compound exhibited weak cytotoxicity against human leukemia (HL‐60) cancer cell with an IG₅₀ value of 63.61 μm , and also antifungal activities against plant pathogenic fungi Rhizoctonia solani and Fusarium oxysporum using standard agar diffusion tests at 20 μg/disk.     

Distributed channel selection in CRAHNs: A non-selfish scheme for mitigating spectrum fragmentation

In this paper, we consider the problem of spectrum sharing in CRAHNs and propose a distributed channel selection scheme. The key functionality of our proposal, best-fit channel selection (BFC) is that it accounts both the primary channel traffic activity and CR traffic activity in channel selection. We assume CR nodes have the capability of estimating the primary channel traffic activities. In BFC, each CR selects a channel among the primary user (PU) channels for transmission that best fits to its transmission time requirement. We compare the performance of BFC to the widely known longest idle time channel selection (LITC) scheme. In LITC, a CR selects the channel that has the longest expected idle time independent of its transmission needs. In a multi-user CRN, this may degrade the network performance compared to the non-selfish BFC approach. LITC is considered selfish since each CR aims to maximize its own benefit and thus wastes resources that may be utilized by other nodes in the network. BFC providing an efficient spectrum sharing mechanism implicitly mitigates the effect of spectrum fragmentation which is a significant issue degrading the CR spectrum utilization. In CRNs, spectrum may be fragmented in various dimensions, e.g. time and frequency, such that some parts of the spectrum can not be used although being idle. Our proposal provides a solution to the spectrum fragmentation issue in time dimension at the medium access control (MAC) layer. By a set of simulations, we highlight the performance improvement by BFC over the conventional LITC under various CR/PU traffic, number of CRs, estimation accuracy and buffering capability. Simulation results show that the performance of the proposed BFC is significantly superior to that of LITC in terms of probability of successful transmission, spectrum opportunity utilization and fragmentation.     

New analytical procedure based on a cellulose bag and ionic exchanger with p-aminobenzoic acid groups for differentiation of labile and inert metal species in aquatic systems

A new procedure was developed for the in situ characterization of the lability of metal species in aquatic systems by using a system equipped with a diffusion membrane and cellulose organomodified with p-aminobenzoic acid groups (DM-Cell-PAB). To this end, the DM-Cell-PAB system was prepared by adding cellulose organomodified with p-aminobenzoic acid groups (Cell-PAB) to pre-purified cellulose bags. After the DM-Cell-PAB system was sealed, it was examined in the laboratory to evaluate the influence of complexation time, mass of exchanger, pH, metal ions (Cu, Cd, Fe, Mn, and Ni), and concentration of organic matter on the relative lability of metal species. It was found that the pH and kinetics strongly influence the process of metal complexation by the DM-Cell-PAB system. At all pH levels, Cd, Mn, and Ni showed lower complexation with Cell-PAB resin than Cu and Fe metals. Note that relative lability of metals complexed to aquatic humic substances (AHS) in the presence of Cell-PAB resin showed the following order: Cu≅Fe≫Ni>Mn=Cd. The results presented here also indicate that increasing the AHS concentration decreases the lability of metal species by shifting the equilibrium to AHS–metal complexes. Our results indicate that the system under study offers an interesting alternative that can be applied to in situ experiments for differentiation of labile and inert metal species in aquatic systems.     

High-throughput purification of combinatorial libraries II: Automated separation of single diastereomers from a 4-amido-pyrrolidone library containing intentional diastereomer pairs

A 4-amido-pyrrolidone library that was intentionally synthesized as pairs of diastereomers was produced by solution-phase parallel syntheses and purified by an automated high-throughput purification system. A total of 2592 4-amido-pyrrolidinones were ultimately isolated as single diastereomers from a matrix of 1920 syntheses. After the four-step synthesis and HPLC purification, the average yield of a single diastereomer was 36.6%. The average chemical purity was >90%, and the average diastereomeric purity was >87%. The choice of chiral amines used to make amides with heterocyclic acid chlorides had a dramatic effect on success. Analysis of the relationship between amines used for synthesis and the diastereomeric separation showed that amides made from chiral 1,2-amino alcohols gave superior separation to amides from chiral morpholines. The presence of a hydrogen bond donor on the amide side chain seems to be required for a better diastereomeric separation.