TBHP/Et3N-Promoted Chemoselective Formylation and Peroxidation of Pyrrolo[2,1-a]isoquinolines.

An efficient formylation of pyrrolo[2,1-a]isoquinoline derivatives has been reached by the use of TBHP (tBuOOH) and Et3N as the mediator. In this strategy, CHO and CDO can be readily incorporated into heteroarenes by the utilization of CHCl3 and CDCl3 as the carbonyl sources. Interestingly, a solvent-controlled chemoselectivity was observed. The use of PhCl as a solvent resulted in dearomatization and peroxidation of pyrrolo[2,1-a]isoquinolines, delivering functionalized peroxides in 53-64% yields.

Synthesis of N-doped and P-doped silicon quantum dots and their applications for tetracycline detection in the honey samples and antibacterial properties.

The abuse of tetracycline can lead to its residue in animal derived foods, posing many potential hazards to human health. Therefore, rapid and accurate detection of tetracycline is an important means to ensure food safety. Nitrogen doped and phosphorus doped silicon quantum dots (N-SiQDs, P-SiQDs) with remarkable optical stability were fabricated via a one-pot hydrothermal procedure in this study. Upon the excitation at 346 nm, N-SiQDs and P-SiQDs emitted fluorescence at 431 nm and 505 nm, respectively. Two SiQDs had the potential to serve as a probe for detecting low concentrations of tetracycline (TC), employing a mechanism of the static quenching effect. The calibration curves of N-SiQDs and P-SiQDs were linear within the range of 0-0.8 µM and 0-0.4 µM, the limits of detection were low as 5.35 × 10-4 µmol/L and 6.90 × 10-3 µmol/L, respectively. This method could be used successfully to detect TC in honey samples. Moreover, the remarkable antibacterial efficacy of two SiQDs could be attributed to the generation of a large number of intracellular reactive oxygen species. The SEM images showed that the structure of bacterial cell was disrupted and the surface became irregular when treated with both SiQDs. These properties enabled potential usage of SiQDs as excellent antibacterial material for different biomedical applications.

Discovery of novel tetrahydrobenzothiophene derivatives as MSBA inhibitors for antimicrobial agents.

The incidence of infections caused by drug-resistant bacteria has been one of the most serious health threats in the past and is substantially increasing in an alarming rate. Therefore, the development of new antimicrobial agents to combat bacterial resistance effectively is urgent. This study focused on the design and synthesis of 40 novel tetrahydrobenzothiophene amide/sulfonamide derivatives and their antibacterial activities were evaluated. Compounds 2p, 6p, and 6 s exhibited significant inhibitory effects on the growth of bacteria. To assess their safety, the cytotoxicity of the compounds was assessed using human normal liver cells, revealing that compound 6p has lower cytotoxicity. A mouse wound healing experiment demonstrated that compound 6p effectively improved wound infection induced by trauma and accelerated the healing process. Compound 6p holds promise as a potential therapeutic agent for combating bacterial infections.

Iron-Catalyzed Synthesis of Peroxylpyrrolo[2,1-a]isoquinolines through Oxidative Dearomatization.

A mild late-stage modification of pyrrolo[2,1-a]isoquinolines was established through iron-catalyzed oxidative dearomatization and peroxidation. Peroxylated pyrroloisoquinolines have been prepared readily with hydroperoxide in low to good yields (up to 72%) at room temperature. Interestingly, the treatment of fully aromatized pyrrolo[1,2-a]quinolines under the current reaction system resulted in the formation of ring-opening products.

A fluorescent probe based on an enhanced ICT effect for Hg2+ detection and cell imaging.

The mercury ion (Hg2+) has hindered society to some extent due to its high biological toxicity, and a rapid method for Hg2+ detection is urgently needed. In the present work, two fluorescent probes, YF-Hg and YF-Cl-Hg, were developed. YF-Cl-Hg was produced by introducing an electron-withdrawing substituent (-Cl) into the structure of YF-Hg. The probe YF-Cl-Hg possesses a larger Stokes shift and a more pronounced UV-vis absorption redshift compared to YF-Hg in a pH = 7.4 environment. The reasons for the superior spectral performance of YF-Cl-Hg over YF-Hg were explored by density functional theory (DFT) calculations and UV-vis absorption spectroscopy. Furthermore, the good biocompatibility suggests that YF-Cl-Hg possesses the potential to be a tool for Hg2+ detection in cells.

The preparation of hybrid silicon quantum dots by one-step synthesis for tetracycline detection and antibacterial applications.

In this study, we prepared three different silicon quantum dots (SiQDs-1, SiQDs-2 and SiQDs-3) by hydrothermal synthesis with rose Bengal as the reducing agent and triacetoxy(methyl)silane and allyloxytrimethylsilane as silicon sources. The as-prepared SiQDs not only exhibited potent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) but also showed specific responses to tetracycline (TC). The minimum inhibitory concentrations (MICs) of SiQDs-1, SiQDs-2 and SiQDs-3 were 0.55 mg mL-1, 0.47 mg mL-1 and 0.39 mg mL-1 against E. coli, respectively, and 0.45 mg mL-1, 0.34 mg mL-1 and 0.34 mg mL-1 against S. aureus, respectively. By examining the morphologies of bacteria and generation of reactive oxygen species (ROS), we speculated that these SiQDs shrink the bacteria and even directly destroy the bacterial structural integrity through the production of singlet oxygen. In addition, the fluorescence quenching effectiveness of SiQDs-3 also showed a strong linear relationship with TC concentration in the range of 0-1.2 µM with a detection limit of 0.318 µM, as a result of the internal filtering effect. Together, SiQDs not only can be a candidate to treat resistant bacterial infections, but also may be applied in practical detection of TC.

Design, synthesis and antibacterial evaluation of a novel class of tetrahydrobenzothiophene derivatives.

In this study, a new series of tetrahydrobenzothiophene derivatives have been designed. Newly designed molecules have been synthesized through a medicinal chemistry route, and their characterization was done by using NMR and HR-MS techniques. Biological evaluation of the synthesized compounds has been done on Gram-negative and Gram-positive bacteria. The marketed antibiotics such as ciprofloxacin and gentamicin were used as controls. The in vitro evaluation results have shown that most of the targeted compounds exhibit good potency in inhibiting the growth of bacteria, including E. coli (MIC: 0.64-19.92 µM), P. aeruginosa (MIC: 0.72-45.30 µM), Salmonella (MIC: 0.54-90.58 µM) and S. aureus (MIC: 1.11-99.92 µM). In particular, compound 3b showed excellent activity with an MIC value of 1.11 µM against E. coli, 1.00 µM against P. aeruginosa, 0.54 µM against Salmonella, and 1.11 µM against S. aureus. From the results, a promising lead compound was identified for future development.

Dual colorimetric and near-infrared fluorescence probe for Hg2+ detection and cell imaging.

Hg2+ in the environment endangers human health, and a convenient monitoring method is needed for the detection of Hg2+. In this study, we constructed a dual colorimetric near-infrared fluorescent probe (E)-2-(3-(3-(1,3-dithian-2-yl)-4-hydroxystyryl)-5,5-dimethylcyclohex-2-en-1-ylidene)malononitrile (YF-Hg), based on the malononitrile isophorone. YF-Hg can detect Hg2+ rapidly and sensitively, with fluorescence emission in the near-infrared region (659 nm) with an obvious color change from violet to red in the visible light range. In addition, the low toxicity and large Stokes shift (191 nm) of YF-Hg also suggest that it is a potential tool for live-cell fluorescence imaging.

Enhanced antibacterial activity with increasing P doping ratio in CQDs.

It is an urgent challenge to develop efficient antibacterial agents against resistant bacteria in the treatment of infectious diseases. Carbon quantum dots (CQDs) have attracted much attention owing to their good stability, low toxicity and excellent biocompatibility. In this work, CQDs doped with different contents of the element phosphorus (P) were prepared by a simple hydrothermal method using valine as a carbon source, triethylamine as a nitrogen source and different volumes of phosphoric acid as a phosphorus source. The average diameter and the surface charge could be regulated from 2.89 nm to 1.56 nm and +2.58 mV to +5.47 mV by increasing the content of the element P in these CQDs. Importantly, these CQDs showed effective bacterial inhibition against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The minimal inhibitory concentration (MIC) decreased from 0.71, to 0.51 to 0.18 mg mL-1 on E. coli and S. aureus with the increase of P element content. Furthermore, the morphologies of E. coli cells and S. aureus were damaged and became irregular upon treatment with these CQDs. The results of singlet oxygen (1O2) detection demonstrated that intracellular 1O2 was generated during the antibacterial process. We speculated that bacterial inhibition induced by these CQDs was accompanied by disruption of permeability and structural integrity, owing to strong electrostatic interactions between negatively charged bacteria and positively charged CQDs and production of singlet oxygen of CQDs. Together, this study indicates that the CQDs can be a candidate to treat resistant bacterial infections and may improve the understanding of killing pathogens by antibacterial CQD drugs.

P-Doped Carbon Quantum Dots with Antibacterial Activity.

It is a major challenge to effectively inhibit microbial pathogens in the treatment of infectious diseases. Research on the application of nanomaterials as antibacterial agents has evidenced their great potential for the remedy of infectious disease. Among these nanomaterials, carbon quantum dots (CQDs) have attracted much attention owing to their unique optical properties and high biosafety. In this work, P-doped CQDs were prepared by simple hydrothermal treatment of m-aminophenol and phosphoric acid with fluorescence emission at 501 nm when excited at 429 nm. The P-doped CQDs showed effective antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The minimal inhibitory concentrations (MICs) of P-doped CQD were 1.23 mg/mL for E. coli and 1.44 mg/mL for S. aureus. Furthermore, the morphologies of E. coli cells were damaged and S. aureus became irregular when treated with the P-doped CQDs. The results of zeta potential analysis demonstrated that the P-doped CQDs inhibit antibacterial activity and destroy the structure of bacteria by electronic interaction. In combination, the results of this study indicate that the as-prepared P-doped CQDs can be a promising candidate for the treatment of bacterial infections.

One-pot synthesis of chlorhexidine-templated biodegradable mesoporous organosilica nanoantiseptics.

Chlorhexidine (CHX) is a widely used antiseptic in various infection control practices. In this work, we have developed biodegradable mesoporous organosilica nanoparticles (MONs) through a one-pot synthesis by employing CHX as a bifunctional agent that not any acts as a cationic template to form the structure of mesopores but also serves as a broad-spectrum antiseptic. The resulting CHX@MONs exhibit a relatively high CHX content and glutathione (GSH)-responsive release of CHX via a matrix-degradation-controlled mechanism, leading to comparable antibacterial effects with CHX on both Escherichia coli and Staphylococcus aureus. Furthermore, the effective antibacterial concentration of CHX@MONs shows less cytotoxicity toward normal cells. Our findings will help increase the use of CHX as an antiseptic agent, especially for responsive drug release upon bacterial infection.

Design, synthesis and in vitro biological evaluation of isoxazol-4-carboxa piperidyl derivatives as new anti-influenza A agents targeting virus nucleoprotein.

Influenza infection is a major cause of morbidity and mortality during seasonal epidemics and sporadic pandemics. It is important and urgent to develop new anti-influenza agents with a new mechanism of action. Nucleozin has been reported as a potent antagonist of nucleoprotein accumulation in the nucleus. In this study, a new series of isoxazol-4-carboxa piperidyl derivatives 1a-j were synthesized and their chemical structures were confirmed by 1H, 13C NMR and mass spectral data. Furthermore, all the synthesized compounds were evaluated for in vitro anti-influenza virus activity against influenza virus (A/PR/8/34 H1N1). Among all the compounds, 1a, 1b, 1c, 1f and 1g exhibited more potent activity than the standard drug, and compound 1b has showed most promising anti-influenza virus activity. These results are also consistent with the docking study results in terms of the design of compounds targeting influenza A via viral nucleoprotein.

Edaravone-Loaded Alginate-Based Nanocomposite Hydrogel Accelerated Chronic Wound Healing in Diabetic Mice.

Refractory wound healing is one of the most common complications of diabetes. Excessive production of reactive oxygen species (ROS) can cause chronic inflammation and thus impair cutaneous wound healing. Scavenging these ROS in wound dressing may offer effective treatment for chronic wounds. Here, a nanocomposite hydrogel based on alginate and positively charged Eudragit nanoparticles containing edaravone, an efficient free radical scavenger, was developed for maximal ROS sequestration. Eudragit nanoparticles enhanced edaravone solubility and stability breaking the limitations in application. Furthermore, loading these Eudragit nanoparticles into an alginate hydrogel increased the protection and sustained the release of edaravone. The nanocomposite hydrogel is shown to promote wound healing in a dose-dependent way. A low dose of edaravone-loaded nanocomposite hydrogel accelerated wound healing in diabetic mice. On the contrary, a high dose of edaravone might hamper the healing. Those results indicated the dual role of ROS in chronic wounds. In addition, the discovery of this work pointed out that dose could be the key factor limiting the translational application of antioxidants in wound healing.

The synthesis of pennogenin 3-O-ß-D-glucopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-ß-D-glucopyranoside.

Pennogenin 3-O-ß-D-glucopyranosyl-(1 → 3)-[α-L-rhamnopyranosyl-(1 → 2)]-ß-D-glucopyranoside, a monodesmosidic saponin isolated from Paris polyphylla Smith var. yunnanensis with promised antitumor activities, was firstly synthesized from glucoside thiol via nine steps and with 27% overall yield.

N-(2,3,4-Trifluoro-phen-yl)pyrrolidine-1-carboxamide.

In the title compound, C(11)H(11)F(3)N(2)O, a urea derivative, the best plane through the pyrrole ring makes a dihedral angle of 9.69 (13)° with the benzene ring. The amino H atom is shielded, so that it is not involved in any hydrogen-bonding inter-actions.

Hourly oral misoprostol administration for terminating midtrimester pregnancies: a pilot study.

OBJECTIVE: This pilot study retrospectively evaluated the outcomes of medical induction of termination of midtrimester pregnancies with hourly oral misoprostol administration. MATERIALS AND METHODS: Sixteen women with living fetuses, who had undergone pregnancy termination at 12-25 weeks of gestational age, were reviewed. The method of induction was hourly oral administration of misoprostol, given at doses of 200 µg/hr for the first 12 hours and 400 µg/hr after 12 hours until delivery. Data including the induction-to-delivery interval and total dosage of misoprostol were recorded and analyzed. RESULTS: All 16 women successfully underwent vaginal termination within 36 hours. The median induction-to-delivery interval was 12.0 hours (range, 6.3-30.9 hours), with 13 women (81.3%) undergoing vaginal delivery within 24 hours. The median total dosage of misoprostol was 2,600 µg. The most common side effect was diarrhea, which was easily relieved by medication. CONCLUSION: Our preliminary results show that oral administration of misoprostol at hourly intervals is a promising method for terminating midtrimester pregnancies.