Moxifloxacin Derivatives with Potential Antibacterial Activity against Methicillin- Resistant Staphylococcus Aureus (MRSA).

BACKGROUND: Methicillin-resistant S. aureus (MRSA) has already tormented humanity and the environment for a long time and is responsible for many difficult-to-treat infections. Unfortunately, there are limited therapeutic options, and MRSA isolates with complete resistance to vancomycin, the first-line drug for the treatment of MRSA infections, have already emerged in recent years. Moxifloxacin retained activity against mutant bacterial strains with various levels of fluoroquinolones resistance and had a lower potential to select for resistant mutants. Isatin is a versatile structure, and its derivatives are potent inhibitors of many enzymes and receptors. The fluoroquinolone- isatin derivatives demonstrated excellent antibacterial activity against both drug-sensitive and drug-resistant organisms. The structure-activity relationship elucidated that incorporation of 1,2,3-triazole moiety into the C-7 position of fluoroquinolone skeleton was favorable to the antibacterial activity. Accordingly, fluoroquinolone derivatives with isatin and 1,2,3-triazole fragments at the side chain on the C-7 position are promising candidates to fight against drug-resistant bacteria. OBJECTIVE: To explore more active moxifloxacin derivatives to fight against MRSA and enrich the structure-activity relationships. METHODS: The synthesized moxifloxacin derivatives 7a-i and 14a-f were evaluated for their antibacterial activity against a panel of MRSA strains by means of standard two-fold serial dilution method. RESULTS: The majority of the synthesized moxifloxacin derivatives were active against most of the tested MRSA strains with MIC values in a range of 1 to 64 µg/mL. The mechanistic investigations revealed that topoisomerase IV was one of the targets for antibacterial activity. CONCLUSION: These derivatives are useful scaffolds for the development of novel topoisomerase IV inhibitors.

Differences of Serum 25- (OH) D3 Level and Adverse Pregnancy Outcomes between Women with Gestational Diabetes and Healthy Pregnant Women.

BACKGROUND: The difference in serum 25-hydroxyvitamin D3 (25-(OH) D3 ) level between the gestational diabetes mellitus (GDM) and healthy pregnant women was analyzed, to provide the experimental evidence for the vitamin supplement in pregnant women, especially those with GDM. METHODS: Pregnant women (n=50) who received prenatal care in the Obstetrical Clinic of Xuzhou Maternity and Child Health Care Hospital in summer and winter of 2016 were enrolled. They were assigned to the summer GDM group, winter GDM group, summer control group and winter control group. The level of serum 25-(OH)D3 was determined using immunochromatography. RESULTS: The mean level of serum 25-(OH)D3 in pregnant women of four groups was lower than normal level. Compared with control group in corresponding season, the winter and summer GDM groups had significantly lower level of 25-(OH)D3 than the winter and summer control groups (P<0.05). The winter GDM group had significantly lower level of 25-(OH)D3 than the summer GDM group (P<0.05). The winter control group had significantly lower level of 25-(OH)D3 than the summer control group (P<0.05). The percentage of deficient 25-(OH)D3 level was the highest in winter GDM group. Vitamin D deficiency was severer in pregnant women with GDM than healthy pregnant women. In winter, vitamin D deficiency was severer than that in summer. CONCLUSION: Pregnant women, especially those with GDM, should pay more attention to vitamin D supplementation.

A Combined Effect of Expression Levels of Obesity-Related Genes and Clinical Factors on Cancer Survival Rate.

Obesity is directly associated with the risk of cancer in different organs, including breast, colon, and kidney. However, adipocytes could be utilized to control progression for some types of cancer, such as leukemia and breast cancer. To explore the potential correlation between adipocytes and cancer, the combined effect of expression levels of obesity-related genes and clinical factors (i.e., gender, race, menopausal status, history of smoking, tumor grade, body mass index (BMI), and history of drinking) on cancer survival rate was systemically studied. The expression levels of obesity-related genes in cancer tissues and normal tissues were downloaded from The Cancer Genome Atlas (TCGA). Kaplan-Meier curves were plotted using R programming language. The log-rank test was applied to explore the correlation between different clinical subgroups. The overexpression of the nine obesity-related genes (MC4R, TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, FTO, PCSK1, and GPR120) may associate with tumor-promoting factors in some organs (head and neck, gastrointestinal tract, liver, and gallbladder). Underexpressed LEPR, NEGR1, TMEM18, and SH2B1 genes prevented the progression and metastasis of kidney cancer. The combined effect of clinical factors and the expression levels of obesity-related genes on patients' survival was found to be significant. Our outcomes suggested that the alternations of DNA methylation patterns could result in the changes of expression levels of obesity-related genes, playing a critical role in tumor progression. The results of the current study may be utilized to supplement precision and personalized medicine, as well as provide novel insights for the development of treatment approaches for cancer.

Ciprofloxacin-1,2,3-triazole-isatin hybrids tethered via amide: Design, synthesis, and in vitro anti-mycobacterial activity evaluation.

The purpose of this study was to prepare various novel amide tethered ciprofloxacin-1,2,3-triazole-isatin hybrids 7a-l, and evaluate their in vitro anti-mycobacterial activity as well as cytotoxicity in VERO cells. The synthesized hybrids showed considerable in vitro activity against both MTB H37Rv and MDR-MTB with MIC of 0.12 to 32 µg/mL, and acceptable cytotoxicity in VERO cells (CC50: 8.0->128.0 µg/mL). In particular, the most active hybrid 7a (MICMTB H37Rv: 0.5 µg/mL and MICMDR-MTB: 0.12 µg/mL) had the activity in the same level with the first-line anti-tubercular agents isoniazid (MIC: 0.12 µg/mL) and rifampicin (MIC: 0.25 µg/mL), and it was 2-fold more active than the parent ciprofloxacin (MIC: 1.0 µg/mL) against MTB H37Rv, and ≥16 folds more potent than ciprofloxacin (MIC: 2.0 µg/mL), isoniazid (MIC: >64 µg/mL) and rifampicin (MIC: >64 µg/mL) against MDR-MTB. Moreover, hybrid 7a (CC50: 16.0 µg/mL) also displayed considerable cytotoxicity towards VERO cells. Thus, hybrid 7a could act as a platform for further investigations.