Naturally Occurring Carbazole Alkaloids from Murraya koenigii as Potential Antidiabetic Agents.

J Nat Prod

Division of Medicinal and Process Chemistry, ‡Division of Biochemistry, §Division of Pharmacokinetics and Metabolism, ∥Sophisticated Analytical Instrument Facility, and ⊥Division of Botany, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.

Published: May 2016

This study identified koenidine (4) as a metabolically stable antidiabetic compound, when evaluated in a rodent type 2 model (leptin receptor-deficient db/db mice), and showed a considerable reduction in the postprandial blood glucose profile with an improvement in insulin sensitivity. Biological studies were directed from the preliminary in vitro evaluation of the effects of isolated carbazole alkaloids (1-6) on glucose uptake and GLUT4 translocation in L6-GLUT4myc myotubes, followed by an investigation of their activity (2-5) in streptozotocin-induced diabetic rats. The effect of koenidine (4) on GLUT4 translocation was mediated by the AKT-dependent signaling pathway in L6-GLUT4myc myotubes. Moreover, in vivo pharmacokinetic studies of compounds 2 and 4 clearly showed that compound 4 was 2.7 times more bioavailable than compound 2, resulting in a superior in vivo efficacy. Therefore, these studies suggested that koenidine (4) may serve as a promising lead natural scaffold for managing insulin resistance and diabetes.

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jnatprod.5b00883DOI Listing

Publication Analysis

Top Keywords

carbazole alkaloids
8
glut4 translocation
8
l6-glut4myc myotubes
8
naturally occurring
4
occurring carbazole
4
alkaloids murraya
4
murraya koenigii
4
koenigii potential
4
potential antidiabetic
4
antidiabetic agents
4

Similar Publications

Euchrestifolines A-O, fifteen novel carbazole alkaloids with potent anti-ferroptotic activity from Murraya euchrestifolia.

Nat Prod Bioprospect

January 2025

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People's Republic of China.

Fifteen novel carbazole alkaloids, euchrestifolines A-O (1-15), were obtained from Murraya euchrestifolia. Their structures were elucidated by spectroscopic analysis, Mosher's ester, calculated ECD, and transition metal complex ECD methods. Notably, euchrestifolines A-C (1-3) are the first naturally occurring pyrrolidone carbazoles to be identified, while euchrestifolines D-F (4-6) represent rare carbazole alkaloids containing a phenylpropanyl moiety; euchrestifoline G (7) features a unique benzopyranocarbazole skeleton.

View Article and Find Full Text PDF

Three-component diels-alder reaction through palladium carbene migratory insertion enabled dearomative C(sp)-H bond activation.

Nat Commun

December 2024

Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, Ministry of Education of China, Key Laboratory of the Assembly and Application of Organic Functional Molecules of Hunan Province, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan, 410081, China.

Owning to the versatile nature in participation of Diels-Alder (D-A) reactions, the development of efficient approaches to generate active ortho-quinodimethanes (o-QDMs) has gained much attention. However, a catalytic method involving coupling of two readily accessible components to construct o-QDMs is lacking. Herein, we describe a palladium carbene migratory insertion enabled dearomative C(sp)-H activation to form active o-QDM species through the cross-coupling of N-tosylhydrazones with aryl halides.

View Article and Find Full Text PDF

The plants of Rutaceae, with wide distribution in China, have a long history of medicinal use. They contain a wide variety of alkaloids, which include isoquinolines, quinolines, acridones, carbazoles, and indoles. Pharmacological studies have shown that most of these alkaloids have antitumor, anti-inflammatory, antiviral, antidiabetic and other activities.

View Article and Find Full Text PDF

Antisense oligonucleotides as a targeted therapeutic approach in model of acute myeloid leukemia.

Mol Biol Rep

December 2024

Laboratory of Tumor Biology and Immunotherapy, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czechia.

Background: The genetic and epigenetic alterations observed in acute myeloid leukemia (AML) contribute to its heterogeneity, influencing disease progression response to therapy, and patient outcomes. The use of antisense oligonucleotides (ASOs) technology allows for the design of oligonucleotide inhibitors based on gene sequence information alone, enabling precise targeting of key molecular pathways or specific genes implicated in AML.

Methods And Results: Midostaurin, a FLT3 specific inhibitor and ASOs targeting particular genes, exons, or mutations was conducted using AML models.

View Article and Find Full Text PDF

Samples from 34 adult patients newly diagnosed with core binding factor leukemia (CBFL) were collected both at the time of diagnosis and at relapse and were centrally analyzed. Eligible patients received either standard induction CT known as "3 + 7" or an equivalent regimen, according to the recruiting center's policy. Patients who achieved CR or CRi received 3 courses of high-dose ARA-C (Cytarabine) 3000 mg/m every 12 h on days 1, 3, and 5, along with midostaurin at the dose of 50 mg b.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!