56254-05-8Relevant articles and documents
Structural Fine-Tuning of Desmuramylpeptide NOD2 Agonists Defines Their in Vivo Adjuvant Activity
Guzelj, Samo,Nabergoj, Sanja,Gobec, Martina,Pajk, Stane,Klan?i?, Veronika,Slütter, Bram,Frkanec, Ru?a,?timac, Adela,?ket, Primo?,Plavec, Janez,Mlinari?-Ra??an, Irena,Jakopin, ?iga
supporting information, p. 7809 - 7838 (2021/06/28)
We report on the design, synthesis, and biological evaluation of a series of nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) desmuramylpeptide agonists with improved in vitro and in vivo adjuvant properties. We identified two promising compounds: 68, a potent nanomolar in vitro NOD2 agonist, and the more lipophilic 75, which shows superior adjuvant activity in vivo. Both compounds had immunostimulatory effects on peripheral blood mononuclear cells at the protein and transcriptional levels, and augmented dendritic-cell-mediated activation of T cells, while 75 additionally enhanced the cytotoxic activity of peripheral blood mononuclear cells against malignant cells. The C18 lipophilic tail of 75 is identified as a pivotal structural element that confers in vivo adjuvant activity in conjunction with a liposomal delivery system. Accordingly, liposome-encapsulated 75 showed promising adjuvant activity in mice, surpassing that of muramyl dipeptide, while achieving a more balanced Th1/Th2 immune response, thus highlighting its potential as a vaccine adjuvant.
Multifunctional diamine AGE/ALE inhibitors with potential therapeutical properties against Alzheimer's disease
Lohou, Elodie,Sasaki, N. André,Boullier, Agnès,Sonnet, Pascal
, p. 702 - 722 (2016/07/26)
An important part of pathogenesis of Alzheimer's disease (AD) is attributed to the contribution of AGE (Advanced Glycation Endproducts) and ALE (Advanced Lipid peroxidation Endproducts). In order to attenuate the progression of AD, we designed a new type of molecules that consist of two trapping parts for reactive carbonyl species (RCS) and reactive oxygen species (ROS), precursors of AGE and ALE, respectively. These molecules also chelate transition metals, the promoters of ROS formation. In this paper, synthesis of the new AGE/ALE inhibitors and evaluation of their physicochemical and biological properties (carbonyl trapping capacity, antioxidant activity, Cu2+-chelating capacity, cytotoxicity and protective effect against in?vitro MGO-induced apoptosis in the model AD cell-line PC12) are described. It is found that compounds 40b and 51e possess promising therapeutic potentials for treating AD.
A Maillard approach to 2-formylpyrroles: Synthesis of magnolamide, lobechine and funebral
Yuen, Tsz-Ying,Eaton, Samantha E.,Woods, Tom M.,Furkert, Daniel P.,Choi, Ka Wai,Brimble, Margaret A.
, p. 1431 - 1437 (2014/03/21)
A convenient synthesis of the traditional medicine constituents magnolamide, lobechine and funebral is described. Construction of the 2-formylpyrrole core of these natural products was achieved by means of a Maillard reaction, involving condensation of the sugar surrogate, dihydropyranone 9, with the requisite primary amines. This approach offers a very direct and general route to the 2-formylpyrrole ring system. The synthesis of the 2-formylpyrrole core found in the traditional medicine constituents, magnolamide, lobechine and funebral, was constructed by a Maillard reaction, involving condensation of the sugar surrogate, dihydropyranone 9, with the requisite primary amines. This approach offers a very direct and general route to the 2-formylpyrrole ring system. Copyright
