6512-13-6Relevant academic research and scientific papers
Synthesis, antimicrobial evaluation, and in silico studies of quinoline—1H-1,2,3-triazole molecular hybrids
Awolade, Paul,Cele, Nosipho,Kerru, Nagaraju,Singh, Parvesh
, p. 2201 - 2218 (2020/06/17)
Abstract: Antimicrobial resistance has become a significant threat to global public health, thus precipitating an exigent need for new drugs with improved therapeutic efficacy. In this regard, molecular hybridization is deemed as a viable strategy to afford multi-target-based drug candidates. Herein, we report a library of quinoline—1H-1,2,3-triazole molecular hybrids synthesized via copper(I)-catalyzed azide-alkyne [3 + 2] dipolar cycloaddition reaction (CuAAC). Antimicrobial evaluation identified compound 16 as the most active hybrid in the library with a broad-spectrum antibacterial activity at an MIC80 value of 75.39?μM against methicillin-resistant S. aureus, E. coli, A. baumannii, and multidrug-resistant K. pneumoniae. The compound also showed interesting antifungal profile against C. albicans and C. neoformans at an MIC80 value of 37.69 and 2.36?μM, respectively, superior to fluconazole. In vitro toxicity profiling revealed non-hemolytic activity against human red blood cells (hRBC) but partial cytotoxicity to human embryonic kidney cells (HEK293). Additionally, in silico studies predicted excellent drug-like properties and the importance of triazole ring in stabilizing the complexation with target proteins. Overall, these results present compound 16 as a promising scaffold on which other molecules can be modeled to deliver new antimicrobial agents with improved potency. Graphic abstract: [Figure not available: see fulltext.].
Amino Acid Hot Spots of Halogen Bonding: A Combined Theoretical and Experimental Case Study of the 5-HT7 Receptor
Kurczab, Rafa,Canale, Vittorio,Sataa, Grzegorz,Zajdel, Pawea,Bojarski, Andrzej J.
supporting information, p. 8717 - 8733 (2018/10/02)
A computational approach combining a structure-activity relationship library of halogenated and the corresponding unsubstituted ligands (called XSAR) with QM-based molecular docking and binding free energy calculations was used to search for amino acids frequently targeted by halogen bonding (hot spots) in a 5-HT7R as a case study. The procedure identified two sets of hot spots, extracellular (D2.65, T2.64, and E7.35) and transmembrane (C3.36, T5.39, and S5.42), which were further verified by a synthesized library of halogenated arylsulfonamide derivatives of (aryloxy)ethylpiperidines. It was found that a halogen bond formed between T5.39 and a bromine atom at 3-position of the aryloxy fragment caused the most remarkable, 35-fold increase in binding affinity for 5-HT7R when compared to the nonhalogenated analog. The proposed paradigm of halogen bonding hot spots was additionally verified on D4 dopamine receptor showing that it can be used in rational drug design/optimization for any protein target.
Synthesis and Investigation of S-Substituted 2-Mercaptobenzoimidazoles as Inhibitors of Hedgehog Signaling
Gr??le, Simone,Susanto, Steven,Sievers, Sonja,Tavsan, Emel,Nieger, Martin,Jung, Nicole,Br?se, Stefan
supporting information, p. 931 - 935 (2017/09/22)
Due to the arising resistance of common drugs targeting the Hedgehog signaling pathway, the identification of new compound classes with inhibitory effect is urgently needed. We were able to identify S-alkylated 2-mercaptobenzoimidazoles as a new compound
DOPAMINE D2 RECEPTOR LIGANDS
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Page/Page column 126, (2016/07/05)
The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0- arrestin pathway and/or on the cAMP pathway.
A practical synthesis of sarpogrelate hydrochloride and in vitro platelet aggregation inhibitory activities of its analogues
Chen, Guo Hua,Wang, Sheng,Wu, Fei Hua
scheme or table, p. 287 - 289 (2010/12/20)
A convenient approach for the preparation of sarpogrelate hydrochloride was developed. Two series of sarpogrelate hydrochloride analogues were designed and synthesized in order to improve their platelet aggregation inhibitory activities, biological tests suggested that these compounds have platelet aggregation inhibitory activities to some extent.
