A novel nano material for anti-cerebral ischaemia: preparation and application of borneol angelica polysaccharide liposomes.

OBJECTIVE: To investigate the preparation of novel nanoliposomes (Borneol Angelica Polysaccharide Liposomes, BAPL) for anti-cerebral ischaemia and verify its curative effects and mechanism. METHODS: By applying a uniform experiment design to investigate the fitting combination of BAPL. Encapsulation Efficiency Evaluation of BAPL Preparation; Particle Size and Surface Potential Evaluation of BAPL Biological activity; Cerebral ischaemia models of rats Evaluation of BAPL curative effects and mechanism. RESULTS: (1) The fitting combination of lecithin, Cholesterol, AP mass and the borneol mass was 60 mg, 60 mg, 45 mg and 5 mg. the highest encapsulation efficiency was 80.4%, the particle size was 179.1 nm, and the surface zeta potential was -17.2 mV. It conforms to the nano-material standards. (2) The results of animal experiments show that: In the BAPL group, the infarct volume of TTC staining was significantly decreased, and the expression levels of NF-κBp65, TLR-4, IL-8, IL-6, IL-1ß in brain tissue were significantly decreased, while the expression levels of ZO-1, ZO-2, IL-10 were significantly increased after cerebral ischaemia-reperfusion. CONCLUSION: BAPL is a novel nano and effective material for anti-cerebral ischaemia.

[Design and Verification of Human Metabolic Measurement System Based on STM32].

A high-precision human metabolic measurement system is designed. The system uses STM32F103 as the main control chip to acquire oxygen, carbon dioxide and flow signals to calculate four quantitative indicators: oxygen consumption(VO2), carbon dioxide production(VCO2), respiratory entropy(RQ) and resting energy metabolism(REE), and finally uses an upper computer to display the calculation results.In this paper, the signal acquisition circuit design was carried out for the oxygen sensor, carbon dioxide sensor and flow sensor, and the validity of the device was verified with the American machine MGCDiagnositcs using Bland-Altman analysis method, and the results showed that the four parameters of VO2,VCO2, RQ and REE of both devices fell in the agreement interval of more than 95%. The device thus provides accurate metabolic measurements and offers an effective tool for the field of general health and clinical nutrition support in China.

2-(4-methyl-thiazol-5-yl) ethyl nitrate maleate-potentiated GABAA receptor response in hippocampal neurons.

AIMS: 2-(4-methyl-thiazol-5-yl) ethyl nitrate maleate (NMZM), a derivative of clomethiazole (CMZ), had been investigated for the treatment of Alzheimer's disease (AD). The beneficial effects of NMZM in AD included reversing cognitive deficit, improving learning and memory as well as neuroprotection. The pharmacological effects of NMZM on GABAA receptors were reported previously; however, the mechanisms were unclear and were explored therefore. RESULTS: In this study, we demonstrated that NMZM improved learning and memory by alleviating scopolamine-induced long-term potentiation (LTP) suppression in the dentate gyrus of rats, indicating that NMZM had protective effects against scopolamine-induced depression of LTP. Next, we investigated the action of NMZM on GABAA receptors in hippocampal neurons and the binding site of NMZM on GABAA receptors. NMZM directly activated GABAA receptors in hippocampal neurons in a weak manner. However, NMZM could potentiate the response of GABAA receptors to GABA and NMZM positively modulated GABAA receptors with an EC50 value of 465 µmol/L at 3 µmol/L GABA while this potentiation at low concentration of GABA (1, 3 µmol/L) was more significant than that at high concentration (10, 30 µmol/L). In addition, NMZM could enhance GABA currents after using diazepam and pentobarbital, the positive modulators of GABAA receptors. NMZM could not affect the etomidate-potentiated GABAA current. It suggested that the binding site of NMZM on GABAA receptors is the same as etomidate. CONCLUSIONS: These results provided support for the neuroprotective effect of NMZM, which was partly dependent on the potentiation of GABAA receptors. The etomidate binding site might be a new target for neuronal protection and for drug development.

An improved efficient synthesis of the antibacterial agent torezolid.

An improved and efficient method for the preparation of torezolid based on Suzuki cross-coupling reaction as the key step was developed on a gram scale in five steps. The total yield was 44% and the optical purity of torezolid by the improved method was above 99%.

Design and synthesis of novel benzimidazole derivatives as anti-tuberculosis agents.

In recent studies some urea derivatives have been identified as potent anti-tuberculosis agents by targeting mycobacterial membrane protein large 3 (MmpL3). However, this compound series as exemplified by AU1235 exhibited poor in vitro pharmacokinetic profile. With AU1235 as the lead, we have identified a novel benzimidazole series as potential anti-tuberculosis agents by using scaffold hopping approach. Among these synthesized compounds, 2-aminobenzimidazole derivative 8b showed the potent anti-tuberculosis activity with the MIC value of 0.03 microg x mL(-1). This compound also showed improved metabolic stability compared to AU1235. Our investigation indicated that benzimidazole derivatives are the promising lead for further optimization as anti-tuberculosis agents.

Synthesis and in vitro antitumor activities of novel benzyl urea analogues of sorafenib.

A novel series of benzyl urea analogues based on the structural modification of sorafenib were synthesized. Their in vitro antitumor activities against MX-1, HepG2, Ketr3 and HT-29 were evaluated using the standard MTT assay. While several target compounds showed inhibitory activity against multiple cancer cell lines, compound 9 was of particular interest, demonstrating IC50 values (5.69-13.6 micromol x L(-1)) comparable to those of sorafenib. Furthermore, compounds 20 and 23 showed more potent inhibitory activity against HT-29 and MX-1 when compared to sorafenib. In particular, compound 20 bearing the N-3-pyridyl moiety not only exhibited greater inhibitory activity against HT-29 cell line (IC50 3.82 micromol x L(-1)), but also had improved solubility at pH 7.2, is worthy of further investigation as a lead to identify novel antitumor agents.

Selection of Vibrio harveyi-resistant Litopenaeus vannamei via a three-round challenge selection with a pathogenic strain of V. harveyi.

To obtain Vibrio harveyi-resistant Litopenaeus vannamei shrimp used for study on immune response of shrimp avoid vibriosis, a three-round challenge selection procedure was applied. In this procedure, resistant shrimp were selected gradually via three rounds challenge experiment with a pathogenic strain of V. harveyi at a median and controllable lethal dose of 96-h LD50 (the median lethal dose). After this procedure, the cumulative mortality of selected shrimp during 96 h after injection of V. harveyi at 2.0 × 10(6) cfu shrimp(-1) significantly decreased from 93.3% to 26.7%, the hours of beginning of death and the hours of attaining of the maximum cumulative mortality of shrimp prolonged from 4 h and 10 h to 8 h and 24 h, respectively. The LD50 of 6 h, 12 h, 24 h, 48 h and 96 h of selected shrimp significantly increased to 1.4 ± 0.1 × 10(7) (p < 0.01), 5.5 ± 0.4 × 10(6) (p < 0.01), 3.1 ± 0.2 × 10(6) (p < 0.01), 2.7 ± 0.1 × 10(6) (p < 0.01) and 2.7 ± 0.1 × 10(6) cfu shrimp(-1) (p < 0.01), about 15.9, 15.3, 9.4, 10.0 and 10.4 times of that of normal shrimp, respectively. In conclusion, the resistance of shrimp to Vibrio significantly increased after the three-round challenge selection procedure.

Synthesis and anti-tubercular activity of novel alkyl substituted riminophenazine derivatives.

A series of novel riminophenazine derivatives bearing an alkyl substituent attached to N-5 and imino nitrogen at C-3 position of the phenazine ring were obtained through rational drug design, aiming to maintain high anti-tubercular activity, lower toxicity and reduce lipophilicity. All target compounds were prepared by utilizing simple and flexible synthetic route and evaluated against Mycobacterium tuberculosis H37Rv and screened for mammalian cytotoxicity. The results demonstrated that compounds with a cyclopropyl substituent at N-5 position were more active than the reference compound clofazimine. In particular, 2-(4-chloroanilino)-5-cyclopropyl-3-(4-methoxycyclohexyl) imino-3, 5-dihydrophenazine (25) was found to be the most potent compound with low cytotoxicity and lipophilicity. This compound could serve as a valuable lead molecule for further optimization.

[Design, synthesis and in vitro activity of glycinamide-bearing compounds as DPP-IV inhibitors].

To research the structure-activity relationship (SAR) of glycinamide-bearing compounds that used as inhibitors of dipeptidyl peptidase IV (DPP-IV), P32/98 and compound A were chosen as the leading compounds, heterocycles containing nitrogen atom were introduced to form amide, and different residues on a-position of carbonyl were designed. The nineteen designed compounds were synthesized by a simple route and were evaluated as inhibitors of DPP-IV. All of the structures were characterized by 1H NMR and HRMS. The preliminary SAR result was obtained.

A novel total synthesis of kinsenoside and goodyeroside A relying on the efficient reaction of the chiral 2(5H)-furanones.

A new total synthesis of the bioactive compounds, kinsenoside and goodyeroside A, has been accomplished from readily available starting materials. The chiral 2(5H)-furanone and its enantiomer were employed as the key chiral intermediates to construct the chiral glycosides and with the appropriate stereochemistry. The spectral data of the target compounds and their acetylated derivatives and are identical with those of the natural and corresponding acetylated products.