Recognition System for Leaf Diseases of Ophiopogon japonicus Based on PCA-SVM

Taking leaf black spot,anthracnose and leaf blight of Ophiopogon japonicus as the research objects,lesions were separated by K-Means clustering segmentation technology.PCA(principal component analysis)was carried out on the 46-dimensional eigenvectors composed of color,shape and texture features,and then the multi-level classifier designed by SVM(support vector machine)was used to identify lesions.The recognition rate of the developed leaf disease recognition system of O.japonicus achieved 93.3%.The results indicates that the system is of great significance to the prevention and control of O.japonicus diseases and the modernization of O.japonicus industry.

Antioxidant Activity of 50 Traditional Chinese Medicinal Materials Varies with Total Phenolics

This study was designed to determine the total phenolic content of 50 herbs and to examine their antioxidant potential. In the sample preparation, 60% ethanol was chosen as the extraction solvent for the subsequent experiments. Folin-Cicolteau phenol reagent and a colorimetric method were used to determine the total phenolic content of the selected herbs. The result showed that total phenolic content of those herbs ranged from 2 to 185 mg/g. In antioxidant assay, the ferric reducing/antioxidant power (FRAP) values ranged from 2 to 134 mg GAE/g;the IC50 values of DPPH?·, ·OH and ?scavenging were in the range of 0.06 - 5.50 mg/mL, 0.017 - 0.636 mg/mL and 0.050 - 0.681 mg/mL respectively. Flos caryophylli was the exceptant in the ?scavenging assay because there was no linear relation between the concentration and the scavenging percentage. Compared to gallic acid, ascorbic acid and butylated hydroxytoluene (BHT) in antioxidant assay as positive control, the most potential antioxidant herbs were Cacumen platycladi, Radix et Rhizoma rhei, Rhizoma rhodiolae crenulatae, and Rhizoma sanguisorbae with considerable content of phenolics. Especially, a positive and significant correlation was found between the total phenolic content and FRAP value or DPPH· scavenging percentage.

左氧氟沙星对质粒介导的喹诺酮类耐药大肠埃希菌的体外PK/PD研究

AIM: Bacterial resistance to quinolones has traditionally mediated by alteration of the quinolone targets and/or overproduction of efflux pump. Recently, a new mechanism, the plasmid-mediated quinolone resistance named qnr, has been clarified. Qnr and its homologus are widely distributed among gram-negative bacteria. The presence of qnr only slightly elevates the resistance level, however it facilitates the selection of highly resistant strains. In our study, we examined the probable influence of such phenomenon to the clinical regimens of levofloxacin. METHODS: In-vitro hollow fiber infection model simulating oral two-compartment pharmacokinetic model was established. In the model, bacteria was incubated in the peripheral compartment without ‘washout effect’. We designed two therapeutic regimens of levofloxacin, including 500 mg qd (peak 5.12 mg/L; half-time 6.9 h) and 700 mg qd (peak 9.46 mg/L; half-time 6.9 h) for 3 days against E.coli J53 and E. coli 6503, which carrying qnr positive plasmid. RESULTS: Although 500 mg qd regimen could decrease the bacteria density of E. coli 6503 at the beginning, the bacteria population bounced back when the drug concentration was drecreased below 2 mg/L, and the regrowth bacteria had higher MICs than the parental strains. 700 mg qd for 3 days could inhibit the outgrowth of E. coli 6503 all the time. E. coli J53 was well inhibited by both the mentioned therapeutic regimens. DNA sequencing found the mutations in QRDR of E. coli 6503. CONCLUSION: We conclude that 500 mg qd which is the most popular regimen is at risk of selecting resistant mutations and treatment failure while treating the infections caused by qnr positive E. coli, and 750 mg qd might be preferred. In vivo pharmacodynamic studies to support our findings are warranted.

吉米沙星片剂单剂及多剂临床药物动力学研究

AIM: To investigate the pharmacokinetics and safety of gemifloxacin in healthy Chinese subjects and provide some theoretic bases for its reasonable application in clinic. METHODS:(1) 12 healthy Chinese male subjects were enrolled in this study with an open label, 3-period cross-over oral single dosing pharmacokinetic study. The subjects sequentially took 3 doses of gemifloxacin (160, 320 and 480 mg) according to the randomization schedule. (2)20 subjects were chosen to participate in a randomized, double blind, multiple dosing pharmacokinetic study. The subjects were orally given 320 mg gemifloxacin or matching placebo once daily for 7 consecutive days. Clinical observation and laboratory test were performed during the study for the assessment of adverse events. The concentrations of gemifloxacin in serum and urine were determined by high performance liquid chromatogram (HPLC). The pharmacokinetic parameters were analysed by 3P97 analysis software. RESULTS: (1)The pharmacokinetic courses following single crossover oral dose of 160, 320 and 480 mg were all in accordance with the two-compartment model. The Cmax were (0.70±0.19), (1.40±0.32) and (1.84±0.35) mg/L, respectively. The mean times to reach Cmax were (1.2±0.4), (1.1±0.4) and (1.4±0.4) h, respectively. The values of t1/2β were (7.0±1.0), (6.7±0.8) and (6.9±0.8) h, respectively. The AUC0-∞ were (4.1±0.6), (7.5±1.1) and (11.7±1.7) mg·L-1·h, respectively. The accumulation urinary excretion at 48 hours post dosing were 39%±69%, 38%±7% and 36%±5%, respectively. The concentrations and AUCs of gemifloxacin had a linear pharmacokinetics with dose manner. (2) The results from multiple dosing of 320 mg for 7 days showed that the pharmacokinetic course following the last dose on day 7 was in accordance with one following the first dose on day 1, which were in accordance with the two-compartment model. The Cmax was (1.6±0.3) mg/L on day 1 and (1.6±0.3) mg/L on day 7. The mean times to reach Cmax were (0.9±0.4) and (1.1±0.3) h, respectively. The values of t1/2β were (6.1±0.8) and (7.8±0.4) h, respectively. The AUC0-∞ on day 7 was significantly higher than that on day 1 (9.40 mg·L-1·h vs 8.23 mg·L-1·h). The accumulation urinary excretion at 48 hours post dosing were 37%±5% and 42%±9%, respectively. The pharmacokinetic parameters had no statistical significance between day 1 and day 7. The mean accumulated factor of AUC on day 7 against on day 1 was 1.13±0.02, suggesting that multiple administrations of 320 mg gemifloxacin once daily for 7 days caused a mild accumulation. (3) One subject was reported with pharyngitis and 3 subjects with dizziness, diarrhea, and tremor after took single oral dose of 160 mg of gemifloxacin. There were no laboratory abnormalities except for two occurrences of slight bilirubinaemia. CONCLUSION: The results show that the pharmacokinetics of single dose and multiple dose of gemifloxacin in healthy Chinese male subjects are linear and major pharmacokinetics parameters on day 7 are similar to those following the first dose on day 1 after subjects taking multiple dosing of 320 mg once daily for 7 days. The data suggest that single and multiple doses of gemifloxacin are well tolerated except that one subject was withdrawn because of rash.

Screening strategies for quorum sensing inhibitors in combating bacterial infections

Interference with quorum sensing(QS)represents an antivirulence strategy with a significant promise for the treatment of bacterial infections and a new approach to restoring antibiotic tolerance.Over the past two decades,a novel series of studies have reported that quorum quenching approaches and the discovery of quorum sensing inhibitors(QSIs)have a strong impact on the discovery of anti-infective drugs against various types of bacteria.The discovery of QSI was demonstrated to be an appropriate strategy to expand the anti-infective therapeutic approaches to complement classical antibiotics and antimicrobial agents.For the discovery of QSIs,diverse approaches exist and develop in-step with the scale of screening as well as specific QS systems.This review highlights the latest findings in strategies and methodologies for QSI screening,involving activity-based screening with bioassays,chemical methods to seek bacterial QS pathways for QSI discovery,virtual screening for QSI screening,and other potential tools for interpreting QS signaling,which are innovative routes for future efforts to discover additional QSIs to combat bacterial infections.

Multicenter Antimicrobial Resistance Surveillance of Clinical Isolates from Major Hospitals—China,2022

What is already known about this topic?Bacterial resistance surveillance is crucial for monitoring and understanding the trends and spread of drug-resistant bacteria.What is added by this report?The number of strains collected in 2022 increased compared to 2021.The top five bacteria,including Escherichia coli,Klebsiella pneumoniae,Staphylococcus aureus,Pseudomonas aeruginosa,and Acinetobacter baumannii,remained largely unchanged.The detection rate of methicillin-resistant strains continued to decrease.Among clinical Enterobacterales isolates,the resistance rate to carbapenems was generally below 13%,except for Klebsiella spp.,which had a resistance range of 20.4%to 21.9%.Most clinical Enterobacterales isolates were highly susceptible to tigecycline,colistin,and polymyxin B,with resistance rates ranging from 0.1%to 12.6%.The detection rate of meropenem-resistant P.aeruginosa and meropenemresistant Acinetobacter baumannii showed a decreasing trend for the fourth consecutive year.What are the implications for public health practice?Multidrug-resistant bacteria remain a significant public health challenge in clinical antimicrobial treatment.To effectively address bacterial resistance,it is essential to enhance both bacterial resistance surveillance and the prudent use of antimicrobial agents.

利奈唑胺片剂在中国男性志愿者中的绝对生物利用度

AIM: Linezolid is a member of oxazolidinones, which is a novel class of antibiotics. The study is to determine the absolute bioavailability of linezolid tablets in Chinese healthy male volunteers. METHODS: A randomized, open cross-over study was conducted in 22 healthy male volunteers, a single oral dose of 600 mg linezolid tablets or IV infusion of 600 mg linezolid were given to subjects, respectively. Blood samples were obtained at different time points and sent to American AvTech laboratories. Plasma concentrations of linezolid were determined by high-performance liquid chromatography (HPLC), pharmacokinetic parameters and absolute bioavailability were calculated. RESULTS: After oral and IV infusion administration of 600 mg linezolid, the elimination half-life (t1/2) was (4.3±1.0) h and (4.4±0.9) h, respectively. The area under plasma concentration-time curve (AUC0-∞) of linezolid were (87±20) μg·mL-1·h and (96±21) μg·mL-1·h, respectively. The absolute oral bioavailability was 93%±23% following single oral dose of 600 mg linezolid tablets. Analyses of two one-sided t tests and 90% confidence interval showed that linezolid tablet and IV formulation are equivalent with respect to AUC. No adverse event was found except one volunteer with transitory mild epigastric pain. CONCLUSION: Linezolid tablets can be completely absorbed; it is equivalent in extent of absorption to its IV formulation.

去甲万古霉素群体药代动力学与药效学研究

AIM: To evaluate the population pharmcokinetics (PPK) and pharmacodynamics(PD) of norvancomycin in patients. METHODS: We enrolled 146 patients who were confirmed or suspected with gram-positive bacterial infections in this study. A PPK model was developed and validated by the analysis of NONMEM software. The PK/PD profiles from the pharmacokinetic parameters in the patients and from MIC values were obtained. An optimal dose regime was calculated by the analyses of the PK/PD model according to the clinical outcomes and bacterial tests. The norvancomycin MICs of clinically isolated strains from the patients population were determined by agar dilution methods. RESULTS: The best model was a two compartment pharmacokinetic model with exponential interindividual error and additive residual error statistical models. The finding of the study indicated that the change in Ccr values had impacts on drug clearance (CL). For example, CL of patients with decreased renal function would be influenced. The increased volume of a peripheral distribution (V2) was observed when norvancomycin was co-administered with diuretics. The logistic stepwise analyses revealed that ratio of AUC24/MIC is a major factor which could significantly determine the clinical outcomes and bacterial eradication for patients. When the ratio of AUC24/MIC was more than 579.90 for Staphylococcus aureus infections or it was more than 637.67 for Enterococcal infections, approximately 95% of patients could achieve cure clinical outcome. CONCLUSION: AUC0-24/MIC should be a major PK/PD parameter to determine efficacy of norvancomycin. An optimized regimen of norvancomycin can be simulated and developed for different subgroups of bacterial infected patients with special physiologic and pathologic features.

Chinese consensus guidelines for therapeutic drug monitoring of polymyxin B,endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society

Polymyxin B,which is a last-line antibiotic for extensively drug-resistant Gram-negative bacterial infections,became available in China in Dec.2017.As dose adjustments are based solely on clinical experience of risk toxicity,treatment failure,and emergence of resistance,there is an urgent clinical need to perform therapeutic drug monitoring(TDM)to optimize the use of polymyxin B.It is thus necessary to standardize operating procedures to ensure the accuracy of TDM and provide evidence for their rational use.We report a consensus on TDM guidelines for polymyxin B,as endorsed by the Infection and Chemotherapy Committee of the Shanghai Medical Association and the Therapeutic Drug Monitoring Committee of the Chinese Pharmacological Society.The consensus panel was composed of clinicians,pharmacists,and microbiologists from different provinces in China and Australia who made recommendations regarding target concentrations,sample collection,reporting,and explanation of TDM results.The guidelines provide the first-ever consensus on conducting TDM of polymyxin B,and are intended to guide optimal clinical use.

Modular synthesis of 1,4-diketones through regioselective bis-acylation of olefins by merging NHC and photoredox catalysis

Efficient and modular synthesis of structurally diverse 1,4-diketones from readily available building blocks represents an essential but challenging task in organic chemistry.Herein,we report a multi-component,regioselective bis-acylation of olefins by merging NHC organocatalysis and photoredox catalysis.With this protocol,a broad range of 1,4-diketones could be rapidly assembled using bench-stable feedstock materials.The robustness of this method was further evaluated by sensitivity screening,and good reproductivity was observed.Moreover,the diketone products could be readily converted into functionalized heterocycles,such as multi-substituted furan,pyrrole,and pyridazine.Mechanistic investigations shed light on the NHC and photoredox dual catalytic radical reaction mechanism.

Safety and clinical efficacy of linezolid in children:a systematic review and meta-analysis

Background We aimed to evaluate the tolerability and efficacy of linezolid in children for treating suspected and diagnosed Gram-positive bacterial infections.Methods A systematic literature search was conducted up to April 23,2021,using linezolid and its synonyms as search terms.Two reviewers independently identified and extracted relevant randomized controlled trials and prospective cohort studies.The extracted studies were included in a single-rate meta-analysis of adverse events and clinical outcomes using random-effects models.Results A total of 1082 articles were identified,and nine studies involving 758 children were included in the meta-analysis.The overall proportion of adverse events was 8.91%[95%confidence interval(CI)=1.64%–36.52%],with diarrhea(2.24%),vomiting(2.05%),and rash(1.72%)being the most common.The incidences of thrombocytopenia and anemia were 0.68%and 0.16%,respectively.Some specific adverse events,including rash and gastrointestinal events,were more frequent in the oral administration subgroup.In terms of efficacy,the overall proportion of clinical improvement was 88.80%(95%CI=81.31%–93.52%).Children with a history of specific bacteriological diagnosis or concomitant antibiotic therapy had a 1.13-fold higher clinical improvement than children without such histories.The proportion of microbial eradication was 92.68%(95%CI=84.66%–96.68%).The proportion of all-cause mortality was 0.16%(95%CI=0.00%–7.75%).Conclusions Linezolid was well-tolerated in pediatric patients and was associated with a low frequency of adverse events,such as anemia,thrombocytopenia,and neutropenia.Moreover,linezolid was effective in children with diagnosed and suspected Gram-positive infections.

Repurposing vitamin D for treatment of human malignancies via targeting tumor microenvironment

Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components.Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. In this review, we have outlined the current knowledge on epidemiological studies and clinical trials of vitamin D. Notably, wesummarized and discussed the anticancer action of vitamin D in cancer cells, cancer stem cells and stroma cells in tumor microenvironment, providing a better understanding of the role of vitamin D in cancer. We presently re-propose vitamin D to be a novel and economical anticancer agent.

Diversity,bioactivities,and metabolic potentials of endophytic actinomycetes isolated from traditional medicinal plants in Sichuan,China

The present study was designed to determine the taxonomic diversity and metabolic activity of the actinomycetes community, including 13 traditional medicinal plants collected in Sichuan province, China, using multiple approaches such as morphological and molecular identification methods, bioactivity assays, and PCR screening for genes involved in antibiotics biosynthesis. 119 endophytic actinomycetes were recovered; 80 representative strains were chosen for 16 S r RNA gene partial sequence analyses, with 66 of them being affiliated to genus Streptomyces and the remaining 14 strains being rare actinomycetes. Antimicrobial tests showed that 12(15%) of the 80 endophytic actinomycetes displayed inhibitory effects against at least one indicator pathogens, which were all assigned to the genus Streptomyces. In addition, 87.5% and 58.8% of the isolates showed anticancer and anti-diabetic activities, respectively. Meanwhile, the anticancer activities of the isolates negatively correlated with their anti-diabetic activities. Based on the results of PCR screening, five genes, PKS-I, PKS-II, NRPS, ANSA, and oxy B, were detected in 55.0%, 58.8%, 90.0%, 18.8% and 8.8% of the 80 actinomycetes, respectively. In conclusion, the PCR screening method employed in the present study was conducive for screening and selection of potential actinomycetes and predicting potential secondary metabolites, which could overcome the limitations of traditional activity screening models.

Antimicrobial resistance and molecular epidemiological characteristics of clinical isolates of Staphylococcus aureus in Changsha area

Background Increasing prevalence of Staphylococcus aureus （S. aureus）, particularly methicillin-resistant S. aureus （MRSA） has been reported in China. In this study, we investigated the drug resistance characteristic, genetic background, and molecular epidemiological characteristic of S. aureus in Changsha. Methods Between January 2006 and December 2008, 293 clinical isolates of S. aureus were collected from 11 hospitals in Changsha and identified by the Vitek-2 system. All the isolates were verified as MRSA by PCR amplification of both femA and mecA genes. K-B disk method was used to test drug sensitivity of S. aureus to antibiotics. Pulsed-field gel electrophoresis （PFGE） was performed for genotypic and homologous analysis of 115 isolates randomly selected from the original 293 clinical S. aureus isolates. Results S. aureus was highly resistant to penicillin, ampicillin, erythromycin, and clindamycin with resistant rates of 96.6%, 96.6%, 77.1%, and 67.2% respectively. All the isolates were susceptible to tecoplanin, vancomycin, and linezolid. MRSA accounted for 64.8% （190/293） of all the S. aureus strains. The 115 S. aureus isolates were clustered into 39 PFGE types by PFGE typing, with 13 predominant patterns （designated types A to M） accounting for 89 isolates. The most prevalent PFGE type was type A （n=56, 48.7%） and 100.0% of type A strains were MRSA. PFGE type A included 13 subtypes, and the most prevalent subtype was subtype A1 （46.4%, 26/56）. Strains with PFGE type A were isolated from eight hospitals （8/11）, and both subtypes A1 and A4 strains were isolated in a university hospital. Conclusions Clinical isolates of S. aureus in Changsha were resistant to multiple traditional antibiotics. There was an outbreak of PFGE type A MRSA in this area and the A1 subtype was the predominant epidemic clone. Dissemination of the same clone was an important reason for the wide spread of MRSA.

Comparative analysis of chemical constituents, antimicrobial and antioxidant activities of ethylacetate extracts of Polygonum cuspidatum and its endophytic actinomycete, Streptomyces sp. A0916

The present study investigated the chemical composition of ethylacetate extracts from an endophytic actinomycete Streptomyces sp. A0916 and its host Polygonum cuspidatum. A comparative analysis of the antimicrobial and antioxidant properties of the extracts was also conducted. 32 compounds of P. cuspidatum and 23 compounds of Streptomyces sp. A0916 were isolated and identified by GC/MS. Antimicrobial activities of the extracts were evaluated using eight microbial strains(3 Gram-positive bacteria, 3 Gram-negative bacteria, and 2 fungi). The Streptomyces sp. A0916 extracts showed a wide range of antimicrobial activities and presented greater antimicrobial effectiveness than the P. cuspidatum extracts. The minimum inhibitory concentration(MIC) of Streptomyces sp. A0916 extracts against the ampicillin-resistant strain Enterococcus faecium SIIA843 was 32 μg·m L-1. Furthermore, the extracts had greater antimicrobial effect against Gram-positive bacteria than Gram-negative bacteria. Finally, the antioxidant activity of the Streptomyces sp. A0916 extracts was equal to that of the P. cuspidatum extracts. In conclusion, our results suggest that the endophytic actinomycetes of the medicinal plants are an important source of bioactive substances.

Antimicrobial activity of topical agents against Propionibacterium acnes： an in vitro study of clinical isolates from a hospital in Shanghai, China

This study aimed to compare the antimicrobial activities of topical agents against Propionibacterium acnes isolated from patients admitted to a hospital in Shanghai, China. The minimal inhibitory concentrations of the cultured P. acnes were determined in accordance with the Clinical and Laboratory Standards Institute. Susceptibilities to clindamycin and erythromycin were compared in terms of gender, age, disease duration, previous treatment, and disease severity. A total of 69 P. acnes strains were isolated from 98 patients （70.41%）. The susceptibility to triple antibiotic ointment （neomycin/bacitracin/polymyxin B） and bacitracin was 100%. The susceptibility to fusidic acid was 92.7%. The resistance rates to neomycin sulfate, erythromycin, and clindamycin were 11.7%, 49.3%, and 33.4%, respectively. The high resistance rate to clindamycin and erythromycin was significantly affected by gender, previous treatment, and disease severity rather than by age and disease duration. Topical antibiotics should not be used separately for long-term therapy to avoid multiresistance. The use of topical antibiotics should be determined by clinicians on the basis of clinical conditions.

Characteristics of blood chemistry, hematology, and lymphocyte subsets in pregnant rhesus monkeys

The present study was designed to characterize the blood chemistry, hematology, and lymphocyte subsets in pregnant rhesus monkeys and provide baseline parameters for future studies of reproductive and developmental toxicity and developmental immunotoxicity. Harem-mating was used in 96 female and 16 male rhesus monkeys. Pregnancy was confirmed on gestation day(GD)18 by ultrasound. The blood samples of rhesus monkeys were collected at various times(20 days before pregnancy and GD20, 100 and 150). The analyses of blood chemistry, hematology, and lymphocyte subsets were performed. Copmpared with 20 days before pregnancy, Significant decreases(P < 0.05) were observed in HCT and RBC on GD20, GD150 and in HGB on GD150, Significant increases in NEUT and decreases in LYMPH on GD20 were observed. Significant decreases in ALB from GD20 to GD150 were observed, significant decreases in TP was observed on GD100. Significant increases in mean GLU were observed on GD20 and GD150 during pregnancy. Significant decreases(P < 0.05) in CD20+ subsets on GD100, GD150 and CD4+/CD8+ ratio on GD150 were observed, The significant changes of MCV, MCHC, RDW-SD, MCV, MONO, ALT, AST, GLB, ALP, TBIL, DBIL, IBIL, GGT, CR-S, URIC, TC, TG and CK were observed during the pregnant period, but no biologic change were observed, There were no significant changes in MCH, RDW-CV, MPV, BUN, CD3+, CD4+ and CD8+ during pregnancy. These data provide a database for preclinical study in rhesus monkeys. Physiological anemia, hyperglycemia, and immune suppression may occur in pregnant rhesus monkey which is similar to that found in human, and it is essential to distinguish the physiological changes from the pharmacological effects in reproductive and developmental toxicity and developmental immunotoxicity studies of pharmaceuticals.

NHC-catalysed retro-aldol/aldol cascade reaction enabling solvent-controlled stereodivergent synthesis of spirooxindoles

An N-heterocyclic carbene(NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-basedβ-hydroxyaldehyde has been developed.The ring opening-closure process enables the diastereodivergent synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters by simply changing the reaction solvents(THF or DCE).The Michael/aldol/retro-aldol/aldol sequential protocol allows the diastereodivergent synthesis of spirocyclopentaneoxindoles from 3-substituted oxindole andα,β-unsaturated aldehyde under the relay catalysis of a chiral secondary amine and an NHC catalyst.Moreover,four stereoisomers of the product can be selectively provided by using different combinations of a chiral secondary amine and a solvent.

Organocatalytic asymmetric synthesis of multifunctionalized α-carboline-spirooxindole hybrids that suppressed proliferation in colorectal cancer cells

Organocatalytic asymmetric[3+3]annulations of isatin-derived MBH carbonates and indolin-2-imines were efficiently achieved.This appears to be the first enantioselective approach for using isatin-derived MBH carbonates as 3C synthons to react with indole-derived C,N-dinucleophiles,yielding a series of multifunctionalized α-carboline-spirooxindole hybrids in good to high yields with high stereoselectivities.

Design,synthesis,and bioassay of 5-epi-aminoglycosides

For the purpose of seeking new antibiotics,researchers usually modify the already-existing ones.However,this strategy has been extensively used and is close to its limits,especially in the case of aminoglycosides,and it is difficult to find a proper aminoglycoside antibiotic for novel modification.In this paper,we reported the design,synthesis,and evaluation of a series of 5-epi-neamine derivatives based on the structural information of bacterial 16S RNA A-site binding with aminoglycosides.Bioassay results showed that our design strategy was feasible.Our study offers a new way to search for structurally novel aminoglycosides.Meanwhile,our study provides valuable structure-activity relationship information,which will lead to better understanding and exploitation of the drug target,and improved development of new aminoglycoside antibiotics.