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

2021 ◽  
Vol 14 (12) ◽  
pp. 1206
Author(s):  
Daniel Ramsbeck ◽  
Nadine Taudte ◽  
Nadine Jänckel ◽  
Stefanie Strich ◽  
Jens-Ulrich Rahfeld ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Drug Targets ◽  
Oral Microbiome ◽  
Oral Disease ◽  
Systemic Diseases ◽  
Glutaminyl Cyclase ◽  
Structure Activity ◽  
Oral Pathogens ◽  
Relationship Of ◽  
Nanomolar Range

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.

scholarly journals Differential Response of Oral Mucosal and Gingival Cells to Corynebacterium durum, Streptococcus sanguinis, and Porphyromonas gingivalis Multispecies Biofilms

2021 ◽  
Vol 11 ◽  
Author(s):  
Ulrike Redanz ◽  
Sylvio Redanz ◽  
Puthalayai Treerat ◽  
Sivaraman Prakasam ◽  
Li-Jung Lin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Porphyromonas Gingivalis ◽  
Inflammatory Responses ◽  
Single Species ◽  
Oral Microbiome ◽  
Host Cells ◽  
Oral Disease ◽  
Streptococcus Sanguinis ◽  
Commensal Species ◽  
Multispecies Biofilms

Polymicrobial interactions with oral mucosal surfaces determine the health status of the host. While a homeostatic balance provides protection from oral disease, a dysbiotic polymicrobial community promotes tissue destruction and chronic oral diseases. How polymicrobial communities transition from a homeostatic to a dysbiotic state is an understudied process. Thus, we were interested to investigate this ecological transition by focusing on biofilm communities containing high abundance commensal species and low abundance pathobionts to characterize the host-microbiome interactions occurring during oral health. To this end, a multispecies biofilm model was examined using the commensal species Corynebacterium durum and Streptococcus sanguinis and the pathobiont Porphyromonas gingivalis. We compared how both single and multispecies biofilms interact with different oral mucosal and gingival cell types, including the well-studied oral keratinocyte cell lines OKF4/TERT-1and hTERT TIGKs as well as human primary periodontal ligament cells. While single species biofilms of C. durum, S. sanguinis, and P. gingivalis are all characterized by unique cytokine responses for each species, multispecies biofilms elicited a response resembling S. sanguinis single species biofilms. One notable exception is the influence of P. gingivalis upon TNF-α and Gro-α production in hTERT TIGKs cells, which was not affected by the presence of other species. This study is also the first to examine the host response to C. durum. Interestingly, C. durum yielded no notable inflammatory responses from any of the tested host cells, suggesting it functions as a true commensal species. Conversely, S. sanguinis was able to induce expression and secretion of the proinflammatory cytokines IL-6 and IL-8, demonstrating a much greater inflammatory potential, despite being health associated. Our study also demonstrates the variability of host cell responses between different cell lines, highlighting the importance of developing relevant in vitro models to study oral microbiome-host interactions.

Antimicrobial Activity of Kaurane Diterpenes against Oral Pathogens

2008 ◽  
Vol 63 (5-6) ◽  
pp. 326-330 ◽  
Author(s):  
Sergio R. Ambrosio ◽  
Niege A. J. C. Furtado ◽  
Dionéia C. R. de Oliveira ◽  
Fernando B. da Costa ◽  
Carlos H. G. Martins ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Lactobacillus Casei ◽  
Periodontal Diseases ◽  
Significant Activity ◽  
Streptococcus Sobrinus ◽  
Methyl Ester Derivative ◽  
Structure Activity ◽  
Structural Differences ◽  
Oral Pathogens ◽  
Relationship Of

Two kaurane diterpenes, ent-kaur-16(17)-en-19-oic acid (KA) and 15-β-isovaleryloxy-entkaur- 16(17)-en-19-oic acid (KA-Ival), isolated from Aspilia foliacea, and the methyl ester derivative of KA (KA-Me) were evaluated against oral pathogens. KA was the most active compound, with MIC values of 10 μg mL-1 against the following microorganisms: Streptococcus sobrinus, Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, and Lactobacillus casei. However, KA did not show significant activity against Streptococcus salivarius and Enterococcus faecalis, with MIC values equal to 100 and 200 μg mL-1, respectively. Our results show that KA has potential to be used as a prototype for the discovery of new effective anti-infection agents against microorganisms responsible for caries and periodontal diseases. Moreover, these results allow to conclude that minor structural differences among these diterpenes significantly influence their antimicrobial activity, bringing new perspectives to studies on the structure-activity relationship of this type of metabolites with respect to caries and periodontal diseases.

Antibacterial Activity of Triterpene Acids and Semi-Synthetic Derivatives against Oral Pathogens

2007 ◽  
Vol 62 (9-10) ◽  
pp. 668-672 ◽  
Author(s):  
Luis C. Scalon Cunha ◽  
Márcio L. Andrade e Silva ◽  
Niege A. J. Cardoso Furtado ◽  
Adriana H. C. Vinhólis ◽  
Carlos H. Gomes Martins ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Ursolic Acid ◽  
Streptococcus Sobrinus ◽  
Triterpene Acids ◽  
Microdilution Method ◽  
Structure Activity ◽  
Oral Pathogens ◽  
Relationship Of ◽  
Synthetic Derivatives

Triterpene acids (ursolic, oleanoic, gypsogenic, and sumaresinolic acids) isolated from Miconia species, along with a mixture of ursolic and oleanolic acids and a mixture of maslinic and 2-α-hydroxyursolic acids, as well as ursolic acid derivatives were evaluated against the following microorganisms: Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, Streptococcus salivarius, Streptococcus sobrinus, and Enterococcus faecalis, which are potentially responsible for the formation of dental caries in humans. The microdilution method was used for the determination of the minimum inhibitory concentration (MIC) during the evaluation of the antibacterial activity. All the isolated compounds, mixtures, and semi-synthetic derivatives displayed activity against all the tested bacteria, showing that they are promising antiplaque and anticaries agents. Ursolic and oleanolic acids displayed the most intense antibacterial effect, with MIC values ranging from 30 μg/mL to 80 μg/mL. The MIC values of ursolic acid derivatives, as well as those obtained for the mixture of ursolic and oleanolic acids showed that these compounds do not have higher antibacterial activity when compared with the activity observed with either ursolic acid or oleanolic acid alone. With regard to the structure-activity relationship of triterpene acids and derivatives, it is suggested that both hydroxy and carboxy groups present in the triterpenes are important for their antibacterial activity against oral pathogens.

Structure–activity relationship of human glutaminyl cyclase inhibitors having an N-(5-methyl-1H-imidazol-1-yl)propyl thiourea template

2013 ◽  
Vol 21 (13) ◽  
pp. 3821-3830 ◽  
Author(s):  
Phuong-Thao Tran ◽  
Van-Hai Hoang ◽  
Shivaji A. Thorat ◽  
Sung Eun Kim ◽  
Jihyae Ann ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Glutaminyl Cyclase ◽  
Structure Activity ◽  
Relationship Of

Structure-activity relationship of (-) mammea A/BB derivatives against Leishmania amazonensis

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
MA Brenzan ◽  
CV Nakamura ◽  
BPD Filho ◽  
T Ueda-Nakamura ◽  
MCM Young ◽  
...  
Keyword(s):  
Structure Activity Relationship ◽  
Leishmania Amazonensis ◽  
Activity Relationship ◽  
Structure Activity ◽  
Relationship Of

Enantioselective Michael Addition of Malonates to Enones

2020 ◽  
Vol 24 (7) ◽  
pp. 746-773
Author(s):  
Péter Bakó ◽  
Tamás Nemcsok ◽  
Zsolt Rapi ◽  
György Keglevich
Keyword(s):  
Michael Addition ◽  
Activity Relationship ◽  
Chalcone Derivatives ◽  
Michael Additions ◽  
Michael Reactions ◽  
Structure Activity ◽  
Cyclic Enones ◽  
Michael Acceptors ◽  
Relationship Of ◽  
Enantioselective Catalysts

: Many catalysts were tested in asymmetric Michael additions in order to synthesize enantioenriched products. One of the most common reaction types among the Michael reactions is the conjugated addition of malonates to enones making it possible to investigate the structure–activity relationship of the catalysts. The most commonly used Michael acceptors are chalcone, substituted chalcones, chalcone derivatives, cyclic enones, while typical donors may be dimethyl, diethyl, dipropyl, diisopropyl, dibutyl, di-tert-butyl and dibenzyl malonates. This review summarizes the most important enantioselective catalysts applied in these types of reactions.

Antineoplastic Activity, Structural Modification, Synthesis and Structure-activity Relationship of Dammarane-type Ginsenosides: An Overview

2019 ◽  
Vol 23 (5) ◽  
pp. 503-516 ◽  
Author(s):  
Qiang Zhang ◽  
Xude Wang ◽  
Liyan Lv ◽  
Guangyue Su ◽  
Yuqing Zhao
Keyword(s):  
Structural Modification ◽  
Gastrointestinal Disease ◽  
Structure Activity Relationship ◽  
Cerebrovascular Diseases ◽  
Activity Relationship ◽  
Cycle Arrest ◽  
Structure Activity ◽  
Wide Range ◽  
Structural Association ◽  
Relationship Of

Dammarane-type ginsenosides are a class of tetracyclic triterpenoids with the same dammarane skeleton. These compounds have a wide range of pharmaceutical applications for neoplasms, diabetes mellitus and other metabolic syndromes, hyperlipidemia, cardiovascular and cerebrovascular diseases, aging, neurodegenerative disease, bone disease, liver disease, kidney disease, gastrointestinal disease and other conditions. In order to develop new antineoplastic drugs, it is necessary to improve the bioactivity, solubility and bioavailability, and illuminate the mechanism of action of these compounds. A large number of ginsenosides and their derivatives have been separated from certain herbs or synthesized, and tested in various experiments, such as anti-proliferation, induction of apoptosis, cell cycle arrest and cancer-involved signaling pathways. In this review, we have summarized the progress in structural modification, shed light on the structure-activity relationship (SAR), and offered insights into biosynthesis-structural association. This review is expected to provide a preliminary guide for the modification and synthesis of ginsenosides.

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