We have designed, synthesized, and evaluated 5-benzylidenerhodanine- and 5-benzylidenethiazolidine-2,4-dione-based compounds as inhibitors of bacterial enzyme MurD with E. coli IC(50) in the range 45-206 μM. The high-resolution crystal structure of MurD in complex with (R,Z)-2-(3-[{4-([2,4-dioxothiazolidin-5-ylidene]methyl)phenylamino}methyl)benzamido)pentanedioic acid [(R)-32] revealed details of the binding mode of the inhibitor within the active site and provides a good foundation for structure-based design of a novel generation of MurD inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jm100285g | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pyridazine and pyridazinone compounds in crops protection: a review.
Mol Divers
December 2024
State Key Laboratory of Green Pesticides, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang, 550025, China.
Pyridazine and pyridazinone belong to the same group of six-membered heterocyclic compounds, and both structurally feature two adjacent nitrogen atoms. Pyridazine and pyridazinone derivatives are frequently used as core structures in the development of new green agrochemicals due to their high activity and environmental friendliness, attracting significant attention from researchers in recent years. Over the past 20 years, significant developments have occurred in the field of pyridazine and pyridazinone derivatives, which exhibit insecticidal, fungicidal, herbicidal, antiviral, and plant growth regulating activities.
View Article and Find Full Text PDFExploring the druggability of the UEV domain of human TSG101 in search for broad-spectrum antivirals.
Protein Sci
January 2025
Department of Physical Chemistry, Institute of Biotechnology, and Unit of Excellence in Chemistry Applied to Biomedicine and Environment, School of Sciences, University of Granada, Granada, Spain.
The ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disruption of TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of host-oriented broad-spectrum antivirals with low susceptibility to resistance. TSG101 is a challenging target characterized by an extended and flat binding interface, low affinity for PTAP ligands, and complex binding energetics.
View Article and Find Full Text PDFConoDL: a deep learning framework for rapid generation and prediction of conotoxins.
J Comput Aided Mol Des
December 2024
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China.
Conotoxins, being small disulfide-rich and bioactive peptides, manifest notable pharmacological potential and find extensive applications. However, the exploration of conotoxins' vast molecular space using traditional methods is severely limited, necessitating the urgent need of developing novel approaches. Recently, deep learning (DL)-based methods have advanced to the molecular generation of proteins and peptides.
View Article and Find Full Text PDFBreaking the resistance: integrative approaches with novel therapeutics against Klebsiella pneumoniae.
Arch Microbiol
December 2024
Infectious Diseases Division, CSIR- Indian Institute of Integrative Medicine, Jammu, 180001, India.
Klebsiella pneumoniae is a leading cause of anti-microbial resistance in healthcare-associated infections that have posed a severe threat to neonatal and wider community. The escalating crises of antibiotic resistance have compelled researchers to explore an innovative arsenal beginning from natural resources to chemical modifications in order to overcome the ever-increasing resistance issues. The present review highlights the drug discovery efforts with a special focus on cutting-edge strategies in the hunt for potential drug candidates against MDR/XDR Klebsiella pneumoniae.
View Article and Find Full Text PDFThe effect of KUS121, a novel VCP modulator, against ischemic injury in random pattern flaps.
PLoS One
December 2024
Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Surgery using skin flaps is essential for soft tissue reconstruction. However, postoperative ischemic injury of the skin flap is a major complication and a top concern after the surgery. Currently, evidence-based drugs to fully prevent ischemic injury are not available.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!