163735-06-6Relevant academic research and scientific papers
Indole Based Weapons to Fight Antibiotic Resistance: A Structure-Activity Relationship Study
Lepri, Susan,Buonerba, Federica,Goracci, Laura,Velilla, Irene,Ruzziconi, Renzo,Schindler, Bryan D.,Seo, Susan M.,Kaatz, Glenn W.,Cruciani, Gabriele
, p. 867 - 891 (2016/02/23)
Antibiotic resistance represents a worldwide concern, especially regarding the outbreak of methicillin-resistant Staphylococcus aureus, a common cause for serious skin and soft tissues infections. A major contributor to Staphylococcus aureus antibiotic resistance is the NorA efflux pump, which is able to extrude selected antibacterial drugs and biocides from the membrane, lowering their effective concentrations. Thus, the inhibition of NorA represents a promising and challenging strategy that would allow recycling of substrate antimicrobial agents. Among NorA inhibitors, the indole scaffold proved particularly effective and suitable for further optimization. In this study, some unexplored modifications on the indole scaffold are proposed. In particular, for the first time, substitutions at the C5 and N1 positions have been designed to give 48 compounds, which were synthesized and tested against norA-overexpressing S. aureus. Among them, 4 compounds have NorA IC50 values lower than 5.0 μM proving to be good efflux pump inhibitor (EPI) candidates. In addition, preliminary data on their ADME (absorption, distribution, metabolism, and excretion) profile is reported.
1H-INDOLE-3-ACETAMIDE SPLA2 INHIBITORS
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, (2008/06/13)
A class of novel 1-indole-3-acetamides represented by the formula; is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty acids.
1H-INDOLE-3-ACETIC ACID HYDRAZIDE SPLA2 INHIBITORS
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, (2008/06/13)
A class of novel 1H-indole-3-acetic acid hydrazides is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty acids (e.g., arachidonic acid) for treatment of conditions such as septic shock
Indole inhibitors of human nonpancreatic secretory phospholipase A2. 2. Indole-3-acetamides with additional functionality
Dillard, Robert D.,Bach, Nicholas J.,Draheim, Susan E.,Berry, Dennis R.,Carlson, Donald G.,Chirgadze, Nickolay Y.,Clawson, David K.,Hartley, Lawrence W.,Johnson, Lea M.,Jones, Noel D.,McKinney, Emma R.,Mihelich, Edward D.,Olkowski, Jennifer L.,Schevitz, Richard W.,Smith, Amy C.,Snyder, David W.,Sommers, Cynthia D.,Wery, Jean-Pierre
, p. 5137 - 5158 (2007/10/03)
As reported in our previous paper, a series of indole-3-acetamides which possessed potency and selectivity as inhibitors of human nonpancreatic secretory phospholipase A2(hnps-PLA2) was developed. The design of these compounds was based on information derived from x-ray crystal structures determined for complexes between the enzyme and its inhibitors. We describe here the further implementation of this structure-based design strategy and continued SAR development to produce indole-3-acetamides with additional functionalities which provide increased interaction with important residues within the enzyme active site. These efforts led to inhibitors with substantially enhanced potency and selectivity.
