Design and synthesis of novel ß-carboline-bisindole hybrids as potential anticancer agents.

We are reporting a short and convenient pathway for the synthesis of novel ß-carboline-bisindole hybrid compounds from relatively cheap and commercially available chemicals such as tryptamine, dialdehydes and indoles. These newly designed compounds can also be prepared in high yields with the tolerance of many functional groups under mild conditions. Notably, these ß-carboline-bisindole hybrid compounds exhibited some promising applications as anticancer agents against the three common cancer cell lines MCF-7 (breast cancer), SK-LU-1 (lung cancer), and HepG2 (liver cancer). The two best compounds 5b and 5g inhibited the aforementioned cell lines with the same range of the reference Ellipticine at less than 2 µM. A molecular docking study to gain more information about the interactions between the synthesized molecules and the kinase domain of the EGFR was performed. Therefore, this finding can have significant impacts on the development of future research in medicinal chemistry and drug discovery.

LiOtBu-promoted synthesis of bis(3-indolyl)methanes by the alkylation of indoles with alcohols under air.

Bis(3-indolyl)methanes (BIMs) are known for their important bioactivities, which include anti-cancer, anti-inflammatory, antibacterial, and antioxidant properties. In this study, we are disclosing a metal catalyst-free synthesis of BIMs in high yields via the alkylation reaction of indoles and alcohols in the presence of lithium tert-butoxide base. Notably, oxygen in air played an important role as an oxidant for the facilitation of this transformation. Interestingly, unactivated aliphatic alcohols could be successfully used as alkylating reagents in the alkylation reactions of indole. Especially, several chemical intermediates detected by GC-MS gave important information about the mechanism insights. This method demonstrated cost and environmental advantages for the development of green processes.

Facile access to 5H-thiazolo[2',3':2,3]imidazo[4,5-b]indole derivatives by two-fold Cu-catalysed C-N coupling reactions.

In four simple steps, a series of 5H-thiazolo[2',3':2,3]imidazo[4,5-b]indole and 11H-benzo[4',5']thiazolo[2',3':2,3]imidazo[4,5-b]indole derivatives were prepared with high yields. The key step in this procedure was demonstrated to be two-fold Cu-catalysed C-N coupling reactions of 5-bromo-6-(2-bromophenyl)imidazo[2,1-b]thiazole and 3-bromo-2-(2-bromophenyl)benzo[d]imidazo[2,1-b]thiazole with various amines.

Insights into Structural Behaviors of Thiolated and Aminated Reduced Graphene Oxide Supports to Understand Their Effect on MOR Efficiency.

It is essential to develop novel catalysts with high catalytic activity, strong durability, and good stability for further application in methanol fuel cells. In this work, we present for the first time the effect of the chemical functional groups (thiol and amine) with different electron affinity in reduced graphene oxide supports on the morphology and catalytic activity of platinum nanoparticles for the methanol oxidation reaction. Hydroxyl groups on graphene oxide were initially brominated and then transformed to the desired functional groups. The good dispersion of metal nanoparticles over functionalized carbon substrates (particle size less than 5 nm) with good durability, even at a limited functionalization degree (less than 7%) has been demonstrated by morphological and structural studies. The durability of the catalysts was much improved via strong coordination between the metal and nitrogen or sulfur atoms. Impressively, the catalytic activity of platinum nanoparticles on aminated reduced graphene oxide was found to be much better than that on thiolated graphene oxide despite the weaker affinity between amine and noble metals. These findings support further developing new graphene derivatives with the desired functionalization for electronics and energy applications..

Practical Synthesis of 1,4-Dihydropyridines on Heterogeneous Sulfonicmodified Silica (SBA-15-SO3H) Catalyst Under Mild Condition.

AIMS: Synthesis of 1,4-Dihydropyridines (1,4-DHP) using heterogeneous catalyst under mild condition. OBJECTIVE: Our objective is to explore new applications of non-metal heterogeneous catalysts in the synthesis of 1,4-DHP derivatives in a greener and more efficient approach. METHODS: A greener and more efficient method for the synthesis of 1,4-DHPs and an asymmetric 1,4-DHP (Felodipine drug) was successfully developed in high yields using a heterogeneous SBA- 15-SO3H catalyst. RESULTS: A series of symmetric 1,4-DHP and an asymmetric 1,4-DHP (Felodipine drug) were successfully prepared in high yields using a heterogeneous SBA-15-SO3H catalyst. CONCLUSION: The catalyst, SBA-15-SO3H, exhibited an efficient catalyst activity for the synthesis of 1,4-DHP derivatives in high yields from the aldehyde, ß-ketoester, and NH4OAc as a nitrogen source under mild conditions and short reaction time. Bronsted acid sites of this solid catalyst were figured out to play a key role in this transformation. Interestingly, our catalyst is air-stable and can be recycled at least 5 times without losing catalytic activity.

Facile iodine-promoted synthesis of bis(1-imidazo[1,5-a]pyridyl)arylmethanes and exploration of applications.

A practical strategy for the iodine-promoted synthesis of bis(1-imidazo[1,5-a]pyridyl)arylmethane and its derivatives has been developed. These compounds exhibit high cytotoxicity toward various cancer cell lines and moreover they are promising ligands for the Cu-catalysed synthesis of quinolines.

Electrochemical preparation of monodisperse Pt nanoparticles on a grafted 4-aminothiophenol supporting layer for improving the MOR reaction.

The methanol oxidation reaction (MOR) has recently gained a lot of attention due to its application in fuel cells and electrochemical sensors. To enhance the MOR, noble metal nanoparticles should be homogeneously dispersed on the electrode surface with the aid of one suitable support. In this work, 4-aminothiophenol (4-ATP) molecules which contain simultaneously amine and thiol groups were electro-grafted onto the electrode surface to provide anchoring sites, limit aggregation and ensure good dispersion of metal nanoparticles. The results showed a high density of platinum nanoparticles (PtNPs) with an average size of 25 nm on the glassy electrode modified with a 4-ATP supporting layer. Consequently, the MOR was improved by 2.1 times with the aid of the grafted 4-ATP layer. The electrochemical sensor based on PtNPs/4-ATP/GCE is able to detect MeOH in a linear range from 1.26 to 21.42 mM with a detection limit of 1.21 mM.

Dietary inclusion of chestnut (Castanea sativa) polyphenols to Nile tilapia reared in biofloc technology: Impacts on growth, immunity, and disease resistance against Streptococcus agalactiae.

A feeding trial was carried out to examine the effects of adding chestnut (Castanea sativa) polyphenols (CSP) on the growth, skin mucus and serum immune parameters of Nile tilapia (Oreochromis niloticus). Five experimental diets with inclusion levels of 0, 1, 2, 4, and 8 g kg-1 of CSP were fed to Nile tilapia fingerlings (12.77 ± 0.17 g fish-1) during an eight-week trial. Fish were analyzed on the fourth and eighth week to determine the influences of CSP on growth, skin mucus, and serum immune parameters. Challenging test versus Streptococcus agalactiae was evaluated at the end of the trial. Fish fed with CSP enriched diets displayed a significant increase (P ≤ 0.05) in growth and a decline in feed conversion ratio (P ≤ 0.05). Similarly, skin mucus and serum immune parameters were significantly increased (P ≤ 0.05) in fish fed CSP with respect to the control. The effects were already evident four weeks after the CSP administration. The disease protection test displayed that the fish's survival rate was significantly higher (P < 0.05) in CSP diets over the control. The relative percentage of survival (RSP) was 62.5, 75.0, 58.3, and 37.5 in fish fed diets contained 1, 2, 4, and 8 g kg-1 CSP, respectively. The best effect on growth, immune response, and disease resistance were shown in Nile tilapia fed with a diet supplementation of 2 g kg-1 CSP.

Identification of bacterial pathogens in cultured fish with a custom peptide database constructed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

BACKGROUND: The majority of infectious diseases of cultured fish is caused by bacteria. Rapid identification of bacterial pathogens is necessary for immediate management. The present study developed a custom Main Spectra Profile (MSP) database and validate the method using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for rapid identification of fish bacterial pathogens. Streptococcus agalactiae, Streptococcus iniae, Aeromonas hydrophila, Aeromonas veronii, and Edwardsiella tarda obtained from diseased fish were used as representative bacterial pathogens in this study. Bacterial peptides were extracted to create a Main Spectra Profile (MSP), and the MSPs of each bacterial species was added into the MALDI Biotyper database. Fifteen additional isolates of each bacterial species were tested to validate the utilized technique. RESULTS: The MSPs of all field isolates were clearly distinguishable, and the MSPs of the same species were clustered together. The identification methodology was validated with 75 bacterial isolates. The reliability and specificity of the method were determined with MALDI Biotyper log score values and matching results with 16 s rDNA sequencing. The species identification using the public MALDI Biotyper library (Bruker MALDI Biotyper) showed unreliable results (log score < 2.000) with 42.67% matching result with the reference method. In contrast, accurate identification was obtained when using the custom-made database, giving log score > 2.115, and a 100% matching result. CONCLUSION: This study demonstrates an effective identification of fish bacterial pathogens when a complete custom-made MSP database is applied. Further applications require a broad, well-established database to accommodate prudent identification of many fish bacterial pathogens by MALDI-TOF MS.

Anorectal Functional Outcomes Following Doppler-Guided Transanal Hemorrhoidal Dearterialization: Evidence from Vietnam.

INTRODUCTION: Doppler-guided transanal hemorrhoidal dearterialization (THD) was considered a less invasive and innovative method to treat hemorrhoidal disease, but it may impact the anal area during dearterialization and mucopexy. Thus, this study aimed to assess any changes in anorectal manometry of grade III and IV hemorrhoidal patients following THD treatment. METHODS: This prospective observational study was conducted with patients who had grades III and IV hemorrhoidal disease. The patients were treated using THD at the Department of Surgery in the National Hospital of Traditional Medicine (Hanoi, Vietnam) between June 2012 and December 2013. Anorectal manometry was performed prior to THD and again between 6 and 12 months following the procedure. RESULTS: A total of 40 patients were enrolled in the study, including 32 with grade III hemorrhoids and 8 with grade IV hemorrhoids. The proportion of male patients (65%) was higher than that of female patients (35%), and the majority of patients (82.5%) were > 40 years old. The mean duration of symptoms prior to treatment was 12.3 years. The mean length of the anal sphincter was unchanged before and after THD (3.64 ± 0.40 cm prior to treatment vs. 3.66 ± 0.48 cm following treatment; p = 0.57). Significant differences in treatment-related changes were detected for all anorectal manometric measurements except maximum squeezing pressure (p < 0.05). No patient showed anal stenosis or fecal incontinence. CONCLUSION: The THD technique did not change the length of the anal sphincter 6 months after hemorrhoid treatment. The values of anal pressure and rectal sensation decreased almost significantly between treatment and the follow-up visit. We suggest that further studies, which include larger sample sizes, should be conducted to confirm THD effectiveness in terms of anorectal functions.

Effect of Vietnamese Fly Ash on Selected Physical Properties, Durability and Probability of Corrosion of Steel in Concrete.

Vietnamese fly ash was used as a partial replacement for ordinary Portland cement in the proportions of 10%, 20% and 40%, while the water to cementitious ratios were kept constant at 0.42, 0.5 and 0.55, respectively, for three groups. The compressive strengths of all mixes were determined up to 90 days. The acid resistance of fly ash concrete was examined by the mass loss and compressive strength loss of 100 × 100 × 100 mm³ cubes immersed in a 10% H2SO4 solution. The probability of steel corrosion in the fly ash concrete was assessed by measuring the half-cell potentials of steel bars within beams dimensions of 100 × 100 × 500 mm³, and the flexural strengths of these beams after 300 days of immersion in a 5% NaCl solution were determined. The results demonstrate that the compressive strength of fly ash concrete is reduced at an early age but increases as the concrete continues to hydrate. The fly ash increases the sulfuric acid resistance of concrete. Fly ash additions have only a limited effect on reducing the risk of probability of corrosion of steel in the concrete. The load capacities of 10% and 20% fly ash reinforced concrete beams are higher than that of the control beams after 300 days immersed in a 5% NaCl solution.

Solid-phase PCR for rapid multiplex detection of Salmonella spp. at the subspecies level, with amplification efficiency comparable to conventional PCR.

Solid-phase PCR (SP-PCR) has attracted considerable interest in different research fields since it allows parallel DNA amplification on the surface of a solid substrate. However, the applications of SP-PCR have been hampered by the low efficiency of the solid-phase amplification. In order to increase the yield of the solid-phase amplification, we studied various parameters including the length, the density, as well as the annealing position of the solid support primer. A dramatic increase in the signal-to-noise (S/N) ratio was observed when increasing the length of solid support primers from 45 to 80 bp. The density of the primer on the surface was found to be important for the S/N ratio of the SP-PCR, and the optimal S/N was obtained with a density of 1.49 × 1011 molecules/mm2. In addition, the use of solid support primers with a short overhang at the 5' end would help improve the S/N ratio of the SP-PCR. With optimized conditions, SP-PCR can achieve amplification efficiency comparable to conventional PCR, with a limit of detection of 1.5 copies/µl (37.5 copies/reaction). These improvements will pave the way for wider applications of SP-PCR in various fields such as clinical diagnosis, high-throughput DNA sequencing, and single-nucleotide polymorphism analysis. Graphical abstract Schematic representation of solid-phase PCR.

A novel lab-on-chip platform with integrated solid phase PCR and Supercritical Angle Fluorescence (SAF) microlens array for highly sensitive and multiplexed pathogen detection.

Solid-phase PCR (SP-PCR) has become increasingly popular for molecular diagnosis and there have been a few attempts to incorporate SP-PCR into lab-on-a-chip (LOC) devices. However, their applicability for on-line diagnosis is hindered by the lack of sensitive and portable on-chip optical detection technology. In this paper, we addressed this challenge by combining the SP-PCR with super critical angle fluorescence (SAF) microlens array embedded in a microchip. We fabricated miniaturized SAF microlens array as part of a microfluidic chamber in thermoplastic material and performed multiplexed SP-PCR directly on top of the SAF microlens array. Attribute to the high fluorescence collection efficiency of the SAF microlens array, the SP-PCR assay on the LOC platform demonstrated a high sensitivity of 1.6 copies/µL, comparable to off-chip detection using conventional laser scanner. The combination of SP-PCR and SAF microlens array allows for on-chip highly sensitive and multiplexed pathogen detection with low-cost and compact optical components. The LOC platform would be widely used as a high-throughput biosensor to analyze food, clinical and environmental samples.

Efficient one-pot synthesis of 5-perfluoroalkylpyrazoles by cyclization of hydrazone dianions.

A highly selective and efficient method for the synthesis of 5-trifluoromethylated and 5-perfluoroalkylated pyrazoles has been developed which relies on the cyclization of hydrazine dianions with ethyl perfluorocarboxylates. The pyrazoles prepared were evaluated as potential inhibitors of alkaline phosphatases, namely human tissue non-specific alkaline phosphatase (h-TNAP) and tissue specific intestinal alkaline phosphatase (IAP). Most pyrazole derivatives inhibited h-IAP more markedly than h-TNAP and had minor effects on nucleotide pyrophosphatase/phosphodiesterases. Therefore, the compounds appear as potential selective inhibitors of h-IAP.

Miniaturization of a micro-optics array for highly sensitive and parallel detection on an injection moulded lab-on-a-chip.

A miniaturised array of supercritical angle fluorescence (SAF) micro-optics embedded in a microfluidic chamber was fabricated by injection moulding. The fabricated chip could enhance the fluorescence signal around 46 times compared to a conventional microscope. Collection of the fluorescence signal from the SAF array is almost independent of the numerical aperture, and the limit of detection was improved 36-fold using a simple and inexpensive optical detection system.

A lab-on-a-chip system with integrated sample preparation and loop-mediated isothermal amplification for rapid and quantitative detection of Salmonella spp. in food samples.

Foodborne disease is a major public health threat worldwide. Salmonellosis, an infectious disease caused by Salmonella spp., is one of the most common foodborne diseases. Isolation and identification of Salmonella by conventional bacterial culture or molecular-based methods are time consuming and usually take a few hours to days to complete. In response to the demand for rapid on line or on site detection of pathogens, in this study, we describe for the first time an eight-chamber lab-on-a-chip (LOC) system with integrated magnetic bead-based sample preparation and loop-mediated isothermal amplification (LAMP) for rapid and quantitative detection of Salmonella spp. in food samples. The whole diagnostic procedures including DNA isolation, isothermal amplification, and real-time detection were accomplished in a single chamber. Up to eight samples could be handled simultaneously and the system was capable to detect Salmonella at concentration of 50 cells per test within 40 min. The simple design, together with high level of integration, isothermal amplification, and quantitative analysis of multiple samples in short time, will greatly enhance the practical applicability of the LOC system for rapid on-site screening of Salmonella for applications in food safety control, environmental surveillance, and clinical diagnostics.

Efficient synthesis of α- and δ-carbolines by sequential Pd-catalyzed site-selective C-C and twofold C-N coupling reactions.

Two concise and efficient approaches were developed for the synthesis of α- and δ-carboline derivatives. The success of the synthesis relies on site-selective Suzuki-Miyaura reactions of 1-chloro-2-bromopyridine or 2,3-dibromopyridine with 2-bromophenylboronic acid and subsequent cyclization with amines which proceeds by twofold Pd-catalyzed C-N coupling reactions.

Novel synthesis of 5-methyl-5,10-dihydroindolo[3,2-b]indoles by Pd-catalyzed C-C and two-fold C-N coupling reactions.

A series of 5,10-dihydroindolo[3,2-b]indoles was successfully prepared by an efficient two-step strategy based on site-selective Pd-catalyzed cross-coupling reaction with N-methyl-2,3-dibromoindole and subsequent cyclization by two-fold Pd-catalyzed C-N coupling with amines. The products show a strong fluorescence.

Palladium catalyzed synthesis and physical properties of indolo[2,3-b]quinoxalines.

A series of indolo[2,3-b]quinoxaline derivatives were efficiently synthesized from 2,3-dibromoquinoxaline by two pathways. A one-pot approach using Pd-catalyzed two-fold C-N coupling and C-H activation reactions gave indolo[2,3-b]quinoxaline derivatives in good yields, but with limited substrate scope. In addition, a two-step approach to indolo[2,3-b]quinoxalines was developed which is based on Pd-catalyzed Suzuki coupling reactions and subsequent annulation by Pd-catalyzed two-fold C-N coupling with aromatic and aliphatic amines. The electrochemical and photochemical properties of indolo[2,3-b]quinoxaline derivatives were investigated. These studies show that 6-(4-methoxyphenyl)-6H-indolo[2,3-b]quinoxaline showed the highest HOMO energy level and lowest band gap.

Efficient synthesis of biscarbazoles by palladium-catalyzed twofold C-N coupling and C-H activation reactions.

A new and efficient strategy for the synthesis of 3,9'- and 2,9'-biscarbazoles was developed. Our strategy relies on the cyclization of 1,1'-biphenyl-2,2'-diyl bis(trifluoromethanesulfonate) with 4- or 3-anisidine, transformation of the methoxy to a triflate group and subsequent oxidative Pd-catalyzed cyclization with various anilines.