Tetrahydroimidazo[4,5-c]pyridine-Based Inhibitors of Porphyromonas gingivalis Glutaminyl Cyclase

Pharmaceuticals

Jens-Ulrich Rahfeld¹  Stefanie Strich¹  Daniel Ramsbeck¹  Nadine Taudte²  Nadine Jänckel²  Mirko Buchholz² 

[1] Fraunhofer Institute for Cell Therapy and Immunology IZI, Department of Drug Design and Target Validation MWT, Weinbergweg 22, 06120 Halle (Saale), Germany;PerioTrap Pharmaceuticals GmbH, Weinbergweg 22, 06120 Halle (Saale), Germany;

关键词: PgQC;    Porphyromonas gingivalis;    periodontitis;    glutaminyl cyclase;   

DOI  :  10.3390/ph14121206

来源: DOAJ

【 摘 要 】

Periodontitis is a severe yet underestimated oral disease. Since it is linked to several systemic diseases, such as diabetes, artheriosclerosis, and even Alzheimer’s disease, growing interest in treating periodontitis has emerged recently. The major cause of periodontitis is a shift in the oral microbiome. A keystone pathogen that is associated with this shift is Porphyromonas gingivalis. Hence, targeting P. gingivalis came into focus of drug discovery for the development of novel antiinfective compounds. Among others, glutaminyl cyclases (QCs) of oral pathogens might be promising drug targets. Here, we report the discovery and structure–activity relationship of a novel class of P. gingivalis QC inhibitors according to a tetrahydroimidazo[4,5-c]pyridine scaffold. Some compounds exhibited activity in the lower nanomolar range and thus were further characterized with regard to their selectivity and toxicity.

【 授权许可】

Unknown