25983-53-3Relevant articles and documents
Identification, synthesis and pharmacological evaluation of novel anti-EV71 agents via cyclophilin A inhibition
Yan, Wenzhong,Qing, Jie,Mei, Hanbing,Nong, Junxiu,Huang, Jin,Zhu, Jin,Jiang, Hualiang,Liu, Lei,Zhang, Linqi,Li, Jian
supporting information, p. 5682 - 5686 (2015/11/24)
In this work, the relationship between cyclophilin A (CypA) and EV71 prompted us to screen a series of small molecular CypA inhibitors which were previously reported by our group. Among them, compounds 1 and 2 were discovered as non-immunosuppressive anti-EV71 agents with an EC50 values of 1.07 ± 0.17 μM and 3.36 ± 0.45 μM in virus assay, respectively, which were desirably for the further study. The subsequent chemical modifications derived a novel class of molecules, among which compound 11 demonstrated the most potent anti-EV71 activity in virus assay (EC50 = 0.37 ± 0.17 μM), and low cytotoxicity (CC50 > 25 μM). The following CypA enzyme inhibition studies indicated that there was not only the enzyme inhibition activity, undoubtedly important, functioning in the antiviral process, but also some unknown mechanisms worked in combination, and the further study is underway in our laboratory. Nevertheless, to the best of our knowledge, compound 11 was probably the most potent small molecular anti-EV71 agent via CypA inhibitory mechanism to date. Consequently, our study provided a new potential small molecule for curing EV71 infection.
Design, synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1)
Ma, Lei,Yang, Zhengyi,Li, Chenjing,Zhu, Zhiyuan,Shen, Xu,Hu, Lihong
experimental part, p. 643 - 648 (2012/04/10)
According to the structural characteristics of isoliquiritigenin from Glycyrrhiza uralensis, a series of hydroxychalcones has been designed, synthesized and evaluated for their in vitro inhibitory activities of β-secretase (BACE1). Structure-activity relationship study suggested that inhibitory activity against BACE1 was governed to a greater extent by the hydroxyl substituent on A-and B-ring of the chalcone, and the most active compound was substituted with four hydroxyl group (17, IC50=0.27 μM).
Synthesis and protein kinase inhibitory activity of balanol analogues with modified benzophenone subunits
Lampe, John W.,Jagdmann Jr., G. Erik,Johnson, Mary George,Lai, Yen-Shi,Lowden, Christopher T.,Lynch, Michael P.,Mendoza, José S.,Murphy, Marcia M.,Wilson, Joseph W.,Ballas, Lawrence M.,Carter, Kiyomi,Biggers, Christopher K.,Darges, James W.,Davis, Jefferson E.,Hubbard, Frederick R.,Stamper, Mark L.,Defauw, Jean M.,Foglesong, Robert J.,Hall, Steven E.,Heerding, Julia M.,Hollinshead, Sean P.,Hu, Hong,Hughes, Philip F.
, p. 2624 - 2643 (2007/10/03)
A series of analogues of the protein kinase C (PKC) inhibitory natural product balanol which bear modified benzophenone subunits are described. The analogues were designed with the goal of uncovering structure -activity features that could be used in the development of PKC inhibitors with a reduced polar character compared to balanol itself. The results of these studies suggest that most of the benzophenone features found in the natural product are important for obtaining potent PKC inhibitory compounds. However, several modifications were found to lead to selective inhibitors of the related enzyme protein kinase A (PKA), and several specific modifications to the polar structural elements of the benzophenone were found to provide potent PKC inhibitors. In particular, it was found that replacement of the benzophenone carboxylate with bioisosteric equivalents could lead to potent analogues. Further, a tolerance for lipophilic substituents on the terminal benzophenone ring was uncovered. These results are discussed in light of recently available structural information for PKA.
