In developing inhibitors of therapeutic target enzymes, significant time and effort are committed to the preparation of large numbers of compounds. In an effort to develop a potent inhibitor of protein tyrosine phosphatase (PTP) 1B as an anti-obesity and/or anti-diabetic agent, we constructed an isoxazolone chemical library by using a simplified procedure that circumvents tedious workup and purification steps. The 10×7 isoxazolone derivatives were synthesized by coupling the two halves of the target compounds. When mixed and heated in test tubes, the precursors produced the reaction products as precipitates. After brief washing, the products were pure enough to be used for enzymatic experiments. With the precursors for the coupling reactions prepared, the 10×7 library compounds could be prepared in a day by using the present protocol. The library compounds thus obtained were examined for their inhibitory activities against PTP1B. Among them, compound C3 was the most potent inhibitor of PTP1B with an IC(50) of 2.3 μM. The in vivo effect of C3 was also examined in an obesity-prone mouse strain. Diet-induced obese (DIO)/diabetic mice were divided into two groups and each group was fed a high-fat diet (HFD) or HFD+C3 for four weeks. The group of C3-fed mice gained significantly less weight relative to the HFD-fed control group during the four weeks of the drug feeding period. In contrast to the anti-obesity effect of C3, no difference was observed in the glycemic control of the HFD and HFD+C3 mice groups.
Background Dengue cases have been continuously reported in Nepal, including some large outbreaks, since its first introduction in 2004. The disease is now expanding towards newer locations above 1400 m high, especially the country's capital city, Kathmandu. In 2019, >14,000 dengue cases including six deaths were reported. This study was aimed at the detection and molecular characterization of dengue virus (DENV) in dengue patients. Methods A total of 451 patients were enrolled in this study. Demographic, clinical and laboratory information was collected from dengue patients. Dengue infection was confirmed by antibody/antigen detection assays followed by RT-PCR analysis. Results The DENV patients showed fever, body ache, headache, myalgia, retro-orbital pain and arthralgia. The platelets were decreased, serum liver enzymes were increased and leucopenia was seen. Out of 195 patients, 111 (57.0%) were positive for DENV RNA by consensus PCR. We found DENV-2, 70 (63.1%) as the predominant serotype responsible for the 2019 outbreak, while DENV-3 was detected in two patients. Conclusion Our findings suggest that DENV-2 was the major serotype causing the 2019 massive outbreak in Nepal. This information will help in disease control programs to understand the molecular epidemiology and its changing trend.
The application of silver nanoparticles in various sectors including health related field is remarkably profound. Nowadays, the research of synthesizing metal nanoparticles (MNPs) using plant extracts is fascinating field as it offers the eco-friendly and cost-effective method for nanoparticle synthesis. In this study, we synthesized silver nanoparticles (AgNPs) using methanolic extract of B.asiatica and C. fistula regarding their ethnomedical importance. The synthesized AgNPs were characterized by UV-Visible spectroscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray diffractometer (XRD). UV-vis spectroscopy exhibited the characteristic Surface Plasmon Peak of silver nanoparticle~420 nm.FTIR data were measured to get a preliminary idea on the functional groups responsible for the stabilization of AgNPs. XRD data confirmed the natural crystal structure with a face centered cubic of AgNPs. The antibacterial activity of biosynthesized AgNPs was assessed by testing promptly available gram-positive Staphylococcus aureus and gram-negative Escherichia coli bacterial strain and antioxidant activity was calculated by DPPH assay. The overall outcomes of the studies concluded that the application of the biogenic synthesis of AgNPs of B. asiaticaas an antioxidant and antibacterial agent is more potent showing IC50 value 65.1±1.30 μg/mL and the highest zone of inhibition 15 mm in diameter against S. aureus.
SA37 inhibits protein tyrosine phosphatase 1B (PTP1B) with a medium potency, and inhibits IκB kinase β (IKKβ) at a submicromolar half-maximal inhibitory concentration. In animal study, SA37 reduced dietinduced weight gain in mice, without significantly ameliorating glucose tolerance and lipid parameters. These observations coincide partly with PTP1B knockout but are inconsistent with IKKβ depletion in mice. The effect of SA37 on high-fat diet (HFD)-induced obese mice was compared with previous results obtained by the authors' group on a series of SA compounds that exhibited different inhibitory potencies toward IKKβ and PTP1B.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.