Concise Synthesis of Broussonone A Jo, Hyeju; Choi, Minho; Viji, Mayavan ...
Molecules (Basel, Switzerland),
09/2015, Volume:
20, Issue:
9
Journal Article
Peer reviewed
Open access
A concise and expeditious approach to the total synthesis of broussonone A, a p-quinol natural compound, has been developed. The key features of the synthesis include the Grubbs II catalyst mediated ...cross metathesis of two aromatic subunits, and a chemoselective oxidative dearomatizationin the presence of two phenol moieties. Especially, optimization associated with the CM reaction of ortho-alkoxystyrenes was also studied, which are known to be ineffective for Ru-catalyzed metathesis reactions under conventional reaction conditions because ortho-alkoxy group could coordinate to the ruthenium center, resulting in the potential complication of catalyst inhibition.
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•Tetrahydroquinolines were evaluated for their anti-inflammatory effects in BV2 cells.•The derivative with N-propionyl substituent (ELC-D-2) exhibited the most potent inhibitory ...effect on LPS-induced production of pro-inflammatory mediators such as IL-6, TNF-α, and NO.•ELC-D-2 attenuated expression levels of iNOS and COX-2 and inhibited migration of LPS-stimulated BV2 cells by suppressing NF-κB translocation and JNK phosphorylation.•ELC-D-2 may be a promising therapeutic candidate to prevent and/or treat various neurodegenerative diseases associated with inflammation.
Novel 1,2,3,4-tetrahydroquinoline derivatives with N-alkanoyl, N-benzoyl, or chlorobenzoyl substituents were designed and synthesized to inhibit nuclear factor-kappa B (NF-κB) known to be involved in the regulation of many immune and inflammatory responses. These compounds have been previously reported to inhibit NF-κB transcriptional activity in Raw 267.4 macrophage cells and exhibit cytotoxicities to several human cancer cell lines (Jo et al., ACS Med. Chem. Lett. 7 (2016) 385–390). Accumulating evidence indicated that NF-κB is also involved in neuroinflammation implicated in many neurodegenerative diseases. Thus, the present study investigated effects of 1,2,3,4-tetrahydroquinoline derivatives on LPS-stimulated inflammatory mediators and cell migration using BV2 microglial cells as a model. We found that seven compounds tested in this study inhibited LPS-induced pro-inflammatory mediators including interleukin-6, tumor necrosis factor-α, and nitric oxide in concentration-dependent manners. Among these compounds, ELC-D-2 exhibited the most potent inhibition without showing significant cytotoxicity. We also found that ELC-D-2 attenuated levels of LPS-induced inducible nitric oxide synthase and cyclooxygenase-2. Moreover, ELC-D-2 inhibited nuclear translocation of NF-κB by suppressing inhibitor of kappa Bα phosphorylation. Furthermore, ELC-D-2 inhibited LPS-induced activation of c-Jun N-terminal kinase (JNK), which was associated with suppression of inflammatory mediators and migration of LPS-treated BV2 cells. Collectively, our findings demonstrate that ELC-D-2 inhibits LPS-induced pro-inflammatory mediators and cell migration by suppressing NF-κB translocation and JNK phosphorylation in BV2 microglial cells. These results suggest that ELC-D-2 might have a beneficial impact on various brain disorders in which neuroinflammation involving microglial activation plays a crucial role in the pathogenesis of these diseases.
A series of novel 4-O-methylhonokiol analogs were synthesized in light of revealing structure–activity relationship for inhibitory effect of COX-2 enzyme. The key strategy of the molecular design was ...oriented towards modification of the potential metabolic soft spots (e.g., phenol and olefin) or by altering the polar surface area via incorporating heterocycles such as isoxazole and triazole. Most of all exhibited the inhibitory effects on COX-2 and PGF1 production but not macrophage NO production. Especially, aryl carbamates 10 and 11 exhibited more potent inhibitory activity against COX-2 and PGF1 production.
Abstract
As a result of COVID-19, older adults have experienced isolation, lost social contacts, and a decrease in connections. A recent study found that “approximately one-quarter of ...community-dwelling older adults are considered to be socially isolated, and 43% of them report feeling lonely.” Various innovative interventions have emerged, including technology-based interventions as a means to reduce social isolation in older adults, particularly as information communication technology (ICT) use is on the rise among this population. However, it remains to be known how these connections are faring for older adults in the pandemic and whether these ICT connections lead to greater or lesser feelings of social connectedness. Thirty-nine (N=39) in-depth semi-structured interviews were conducted to explore the lived experiences of technology use among older adults during COVID-19. Participants experiences with ICT ranged from illiterate to savvy. Most participants indicated Zoom was the primary means to stay socially connected to family and friends. Participants emphasized that ICT may be a possible solution to deal with loneliness for those older adults who are especially isolated due to COVID-19 restrictions. Barriers and challenges to ICT use included taking too much time to use and needing help to fix any problems that arose. Finally, participants shared essential aspects of ICT use, revealing that it was ‘technology or nothing.’ Findings from this study indicate a need for a simple ICT for the older adult population. Moreover, findings suggest opportunities for peer-support ICT training programs for older adults.
Two new melampolide-type sesquiterpene lactones, 8β-epoxyangeloyloxy-9α-ethoxy-14-oxo-acanthospermolide (1) and 8β-angeloyloxy-9α-ethoxy-14-oxo-acanthospermolide (2), were isolated from the leaves of ...yacon Smallanthus sonchifolia (POEPP. et ENDL.) H. Robinson along with eleven known melampolides, allo-schkuhriolide (3), enhydrin (4), polymatin A (5), fluctuanin (6), 8β-angeloyloxy-9α-acetoxy-14-oxo-acanthospermolide (7), 8β-angeloyloxy-14-oxo-acanthospermolide (8), 8β-methacryloyloxymelampolid-14-oic acid methyl ester (9), uvedalin (10), polymatin B (11), 8β-tigloyloxymelampolid-14-oic acid methyl ester (12), and sonchifolin (13). Their structures were established on the basis of spectroscopic evidence including 1D- and 2D-NMR experiments. All isolates were evaluated for inhibition of LPS-induced nitric oxide production in murine macrophage RAW 264.7 cells.
Arteminolides B-D (2-4), new farnesyl protein transferase inhibitors, were isolated together with a known arteminolide A (1) and new regioisomers (5-7) of the compounds from the aerial parts of ...Artemisia argyi. Structures of these compounds were elucidated by spectroscopic methods and chemical conversion. Arteminolides inhibited the farnesyl protein transferase with IC(50) values of 0.7-1 microM, while the regioisomers 5-7 were inactive. In addition, it was proved that the exocyclic double bond of sesquiterpene lactone did not affect the inhibitory activity of arteminolide. The effects of compound 2 on H-Ras processing and cellular growth in H-ras-transformed cells were also evaluated.
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