Laboratoire d'Innovation Moléculaire et Applications, Université de Haute-Alsace, Université de Strasbourg, CNRS, 68093 Mulhouse, France.
Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Telangana, India.
Molecules. 2018 Oct 11;23(10):2607. doi: 10.3390/molecules23102607.
The synthesis of racemic substituted 7-amino-5,7,8,9-tetrahydrobenzocyclohepten-6-one hydrochlorides was optimized to enhance reproducibility and increase the overall yield. In order to investigate their specificity, series of enzyme inhibition assays were carried out against a diversity of proteases, covering representative members of aspartic, cysteine, metallo and serine endopeptidases and including eight members of the monometallic M1 family of aminopeptidases as well as two members of the bimetallic M17 and M28 aminopeptidase families. This aminobenzosuberone scaffold indeed demonstrated selective inhibition of M1 aminopeptidases to the exclusion of other tested protease families; it was particularly potent against mammalian APN and its bacterial/parasitic orthologues PepN and AM1.
对消旋取代的 7-氨基-5,7,8,9-四氢苯并环庚烯-6-酮盐酸盐的合成进行了优化，以提高重现性并增加总收率。为了研究它们的特异性，对一系列的蛋白酶抑制实验进行了研究，涵盖了天冬氨酸、半胱氨酸、金属和丝氨酸内肽酶的代表性成员，以及单金属 M1 家族的 8 种氨肽酶和双金属 M17 和 M28 氨肽酶家族的 2 种成员。这种氨基苯并环庚烯酮支架确实对 M1 氨肽酶具有选择性抑制作用，排除了其他测试的蛋白酶家族；它对哺乳动物 APN 及其细菌/寄生虫同源物 PepN 和 AM1 具有特别强的抑制作用。
