A series of potent amide linked PPARgamma/delta dual agonists (1a) has been discovered through rational design. In the ZDF rat model of type 2 diabetes, compound (R)-3-[4-(3-{1-[(5-chloro-1,3-dimethyl-1H-indole-2-carbonyl)-amino]-ethyl}-5-fluoro-phenoxy)-2-ethyl-phenyl]-propionic acid (42) from this series has demonstrated glucose lowering efficacy comparable to the marketed PPARgamma agonist rosiglitazone with less weight gain.
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http://dx.doi.org/10.1016/j.bmcl.2007.10.047 | DOI Listing |
Arch Pharm (Weinheim)
January 2025
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
New derivatives 6a-m with benzimidazole-indole-amide scaffold were developed, synthesized, and assessed for potential inhibitory effects on α-glucosidase and acetylcholinesterase (AChE). These compounds were synthesized by various amine derivatives. With the exception of two compounds, the α-glucosidase inhibitory activities of the title derivatives were more than that of the positive control acarbose.
View Article and Find Full Text PDFBiomater Sci
December 2024
Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China.
Wound healing is a dynamic and complex process involving hemostasis, inflammation, fibroblast proliferation, and tissue remodeling. This process is highly susceptible to bacterial infection, which often leads to impaired and delayed wound repair. While antibiotic therapy remains the primary clinical approach for treating bacteria-infected wounds, its widespread use poses a significant risk of developing bacterial resistance.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of General Medicine, the Second Affiliated Hospital of Xi'an Jiaotong University, Xinjiang Hospital, Urumqi, China.
Among the diabetes-related complications, diabetic nephropathy is the major complication and it leads to end-stage renal failure. In the current investigation, we examined the protection of brucine, an alkaloid extracted from the seeds of Strychnos nux vomica plant widely used in traditional Chinese and Indian medicines against diabetic-induced nephropathy. Male Wistar rats were divided into four groups: control, diabetic rats, diabetic-induced + 40 mg/kg brucine-treated rats, and diabetic-induced + 25 mg/kg metformin-treated rats.
View Article and Find Full Text PDFChem Biodivers
December 2024
Guangxi University, School of Chemistry and Chemical Engineering, No.100, East Daxue Road, Nanning, CHINA.
In order to develop new antifungal molecules and explore further applications of natural products, 25 novel amide-urea compounds were synthesized from anethole in this work by a few simple reactions, and structural confirmation was conducted using 1H-NMR, 13C-NMR, HRMS, and FT-IR. Preliminary bioactivity tests were performed against eight plant pathogens. The results demonstrated that all compounds exhibited antifungal activity against the tested fungi, and 5p exhibited the most potent antifungal activity.
View Article and Find Full Text PDFChemMedChem
December 2024
Novartis Institutes for BioMedical Research Basel, Global Discovery Chemistry, SWITZERLAND.
The pro-inflammatory cytokine interleukin-17A (IL-17) plays an important role in the body's defense against bacterial and fungal infections. However, overexpression of IL-17 has been associated with several diseases, including rheumatoid arthritis, asthma, psoriasis, and even cancer. The role of IL-17 in psoriasis has been confirmed by clinical use of IL-17 antibodies, e.
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