Ring-opening of cyclic sulfamidates with propargylic sulfonamides yielded substrates for a gold-catalyzed cyclization to yield tetrahydropyrazines. Manipulation of the tetrahydropyrazines, by reduction or using multicomponent reactions, yielded piperazine scaffolds in which substitution of the carbon atoms was varied. Such scaffolds may have value in the synthesis of novel screening compounds with lead-like molecular properties.
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Sci Rep
December 2024
Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea.
Articular cartilage has a limited regenerative capacity, resulting in poor spontaneous healing of damaged tissue. Despite various scientific efforts to enhance cartilage repair, no single method has yielded satisfactory results. With rising drug development costs, drug repositioning has emerged as a viable alternative.
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January 2025
State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China; Ningbo Institute of Marine Medicine, Peking University, Beijing 100191, PR China. Electronic address:
Prenylated indole diketopiperazines represent a diverse array of alkaloids with complex chemical scaffolds and with a wide range of biological activities. Aiming to discover bioactive metabolites with structural novelty, genomic annotation in association with the MS/MS-based molecular networking demonstrated a deep-sea derived fungus Aspergillus puulaauensis F77 containing a profile of diketopiperazines. Targeted separation of the cultured fungus led to the isolation of 19 undescribed austamide-type diketopiperazines namely versicoines A-S.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2024
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. Electronic address:
Tissue transglutaminase (TG2) is a multifunctional protein that can catalyze the cross-linking between proteins, and function as a G-protein. TG2's unregulated behaviour has been associated with fibrosis, celiac disease and cancer metastasis. Recently, small molecule irreversible inhibitors have been designed, bearing an electrophilic warhead that can react with the catalytic cysteine, abolishing TG2's catalytic and G-protein capabilities.
View Article and Find Full Text PDFEur J Med Chem
January 2025
University of Catania, Dipartimento di Scienze del Farmaco e della Salute, Viale A. Doria 6, 95125, Catania, Italy. Electronic address:
The design and synthesis of a series of piperidine and piperazine-based derivatives as selective sigma receptor (SR) ligands associated with analgesic activity, are the focus of this work. In this study, affinities at S1R and S2R were measured, and molecular modeling studies were performed to investigate the binding pose features. The most promising compounds were subjected to in vitro toxicity testing and subsequently screened for in vivo analgesic properties.
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December 2024
Natural and Medical Sciences Research Center, University of Nizwa, P. O. Box 33, Birkat Al Mauz, Nizwa, Oman. Electronic address:
In this study, a series of fifteen compounds (7a-o) based on a quinoline-benzimidazole scaffold bearing piperazine acetamide derivatives were synthesized and evaluated for their potential as α-glucosidase inhibitors, which are important therapeutic agents in the management of type 2 diabetes mellitus. Among the synthesized compounds, 7m exhibited the most potent inhibitory activity, demonstrating a 28-fold greater efficacy than the standard clinical inhibitor, acarbose. Molecular docking studies indicated strong binding interactions between 7m and the α-glucosidase active site, including hydrogen bonding, π-π stacking, and π-cation interactions.
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