2538-98-9Relevant articles and documents
A chalcone derivative, 1m-6, exhibits atheroprotective effects by increasing cholesterol efflux and reducing inflammation-induced endothelial dysfunction
Chen, Liv Weichien,Tsai, Min-Chien,Chern, Ching-Yuh,Tsao, Tien-Ping,Lin, Feng-Yen,Chen, Sy-Jou,Tsui, Pi-Fen,Liu, Yao-Wen,Lu, Hsien-Jui,Wu, Wan-Lin,Lin, Wei-Shiang,Tsai, Chien-Sung,Lin, Chin-Sheng
, p. 5375 - 5392 (2020)
Background and Purpose: Atherosclerosis, resulting from lipid dysregulation and vascular inflammation, causes atherosclerotic cardiovascular disease (ASCVD), which contributes to morbidity and mortality worldwide. Chalcone and its derivatives possess beneficial properties, including anti-inflammatory, antioxidant and antitumour activity with unknown cardioprotective effects. We aimed to develop an effective chalcone derivative with antiatherogenic potential. Experimental Approach: Human THP-1 cells and HUVECs were used as in vitro models. Western blots and real-time PCRs were performed to quantify protein, mRNA and miRNA expressions. The cholesterol efflux capacity was assayed by 3H labelling of cholesterol. LDL receptor knockout (Ldlr?/?) mice fed a high-fat diet were used as an in vivo atherogenesis model. Haematoxylin and eosin and oil red O staining were used to analyse plaque formation. Key Results: Using ATP-binding cassette transporter A1 (ABCA1) expression we identified the chalcone derivative, 1m-6, which enhances ABCA1 expression and promotes cholesterol efflux in THP-1 macrophages. Moreover, 1m-6 stabilizes ABCA1 mRNA and suppresses the expression of potential ABCA1-regulating miRNAs through nuclear factor erythroid 2-related factor 2 (Nrf2)/haem oxygenase-1 (HO-1) signalling. Additionally, 1m-6 significantly inhibits TNF-α-induced expression of adhesion molecules, vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1), plus production of proinflammatory cytokines via inhibition of JAK/STAT3 activation and the modulation of Nrf2/HO-1 signalling in HUVECs. In atherosclerosis-prone mice, 1m-6 significantly reduces lipid accumulation and atherosclerotic plaque formation. Conclusion and Implications: Our study demonstrates that 1m-6 produces promising atheroprotective effects by enhancing cholesterol efflux and suppressing inflammation-induced endothelial dysfunction, which opens a new avenue for treating ASCVD. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc.
Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines
Lakó, ágnes,Mendon?a, Ricardo,Molnár, Zsófia,Poppe, László
, p. 40894 - 40903 (2020/11/23)
Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with (R)-transaminase activity for the synthesis of novel disubstituted 1-phenylpropan-2-amines. After optimisation of the asymmetric synthesis, the (R)-enantiomers could be produced with 88-89% conversion and >99% ee, while the (S)-enantiomers could be selectively obtained as the unreacted fraction of the corresponding racemic amines in kinetic resolution with >48% conversion and >95% ee. This journal is
Design and total synthesis of Mannich derivatives of marine natural product lamellarin D as cytotoxic agents
Shen, Li,Xie, Nan,Yang, Bo,Hu, Yongzhou,Zhang, Yongmin
, p. 807 - 817 (2014/10/15)
Enlightened by the modification route from Camptothecin (CPT) to Topotecan and based on classical drug design theory, a series of Mannich derivatives of lamellarin D were designed and synthesized in 26-27 steps starting from vanillin and isovanilin. All synthesized compounds were then biologically evaluated for their in vitro anti-cancer activities and Topo I inhibitory activities. The results showed that most target compounds exhibited Topo I inhibitory activities in equivalent level with that of lamellarin D. Compound SL-9 exhibited better Topo I inhibitory activity than that of lamellarin D. Compounds SL-2, SL-3, SL-4, SL-5 and SL-11 exhibited better anti-proliferative activity against HT-29 cells than that of lamellarin D.
