Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Starting from the analysis of the hypothetical binding mode of our previous furan-based hit (I), we successfully achieved our objective to replace the nitro moiety, leading to the disclosure of a new lead exhibiting a strong activity against MbtI. Our best candidate 1 h displayed a K of 8.8 µM and its antimycobacterial activity (MIC = 250 µM) is conceivably related to mycobactin biosynthesis inhibition. These results support the hypothesis that 5-phenylfuran-2-carboxylic derivatives are a promising class of MbtI inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427685 | PMC |
| http://dx.doi.org/10.1080/14756366.2019.1589462 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nanoenabling MbtI Inhibitors for Next-Generation Tuberculosis Therapy.
J Med Chem
March 2025
Department of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milano, Italy.
The urgent need for safer and innovative antitubercular agents remains a priority for the scientific community. In pursuit of this goal, we designed and evaluated novel 5-phenylfuran-2-carboxylic acid derivatives targeting () salicylate synthase (MbtI), a key enzyme, absent in humans, that plays a crucial role in virulence. Several potent MbtI inhibitors demonstrating significant antitubercular activity and a favorable safety profile were identified.
View Article and Find Full Text PDFStructural Study of a New MbtI-Inhibitor Complex: Towards an Optimized Model for Structure-Based Drug Discovery.
Pharmaceuticals (Basel)
November 2023
Institut Pasteur, Université Paris Cité, CNRS UMR3528, Unité de Microbiologie Structurale, F-75015 Paris, France.
Article Synopsis
- MbtI is a magnesium-dependent enzyme critical for iron acquisition in tuberculosis pathogens, making it a promising target for new anti-virulence therapies.
- Recent studies identified 5-phenylfuran-2-carboxylic acids as effective inhibitors of MbtI, with the first crystal structure of the enzyme-inhibitor complex published in 2020 revealing its open configuration.
- A new high-resolution crystal structure shows MbtI in a closed conformation with a furan derivative, allowing for a complete view of the active site, and indicates that the effectiveness of inhibitors may not depend on the enzyme's conformation.
Targeting iron-scavenging tools: a recent update on siderophores inhibitors.
RSC Med Chem
October 2023
Department of Natural Products, Chemical Sciences, National Institute of Pharmaceutical Education and Research-Hyderabad (NIPER-Hyderabad) Balanagar Hyderabad 500037 India
Among the various bacterial infections, tuberculosis (TB) remains a life-threatening infectious disease responsible as the most significant cause of mortality and morbidity worldwide. The co-infection of human immunodeficiency virus (HIV) in association with TB burdens the healthcare system substantially. Notably, possesses defence against most antitubercular antibiotic drugs, and the efficacy of existing frontline anti-TB drugs is waning.
View Article and Find Full Text PDFTargeting Siderophore-Mediated Iron Uptake in : A New Strategy to Limit the Virulence of Non-Tuberculous Mycobacteria.
Pharmaceutics
February 2023
Department of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milano, Italy.
Targeting pathogenic mechanisms, rather than essential processes, represents a very attractive approach for the development of new antimycobacterial drugs. In this context, iron acquisition routes have recently emerged as potentially druggable pathways. However, the importance of siderophore biosynthesis in the virulence and pathogenicity of () is still poorly understood.
View Article and Find Full Text PDFSynthesis and Assessment of the In Vitro and Ex Vivo Activity of Salicylate Synthase (Mbti) Inhibitors as New Candidates for the Treatment of Mycobacterial Infections.
Pharmaceuticals (Basel)
August 2022
Department of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milano, Italy.
Tuberculosis (TB) causes millions of deaths every year, ranking as one of the most dangerous infectious diseases worldwide. Because several pathogenic strains of () have developed resistance against most of the established anti-TB drugs, new therapeutic options are urgently needed. An attractive target for the development of new anti-TB agents is the salicylate synthase MbtI, the first enzyme of the mycobacterial siderophore biochemical machinery, absent in human cells.
View Article and Find Full Text PDF