Protein phosphatases have recently emerged as important targets for research in chemical biology and medicinal chemistry, and new classes of phosphatase inhibitors are in high demand. BIOS (biology-oriented synthesis) employs the criteria of relevance to nature and biological prevalidation for the design and synthesis of compound collections. In an application of the BIOS principle, an efficient solid-phase synthesis of highly substituted indolo[2,3-a]quinolizidines by using a vinylogous Mannich-Michael reaction in combination with phosgene- or acid-mediated ring closure was developed. Screening of this library for phosphatase inhibitors yielded a new inhibitor class for the Mycobacterium tuberculosis phosphatase MptpB.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/asia.200700125 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Combating Tuberculosis via Restoring the Host Immune Capacity by Targeting Kinases and Phosphatases.
Int J Mol Sci
November 2024
Curtin Medical School, Faculty of Health Sciences, Curtin University, Bentley, Perth, WA 6102, Australia.
() is a remarkably versatile pathogen that possesses a unique ability to counteract the host's defence mechanisms to control the infection. Several mycobacterial protein kinases and phosphatases were found to play a key role in impeding phagosome maturation in macrophages and accordingly blocking the phagosome-lysosome fusion, therefore allowing the bacteria to survive. During phagocytosis, both and the host's phagocytic cells develop mechanisms to fight each other, resulting in pathogen elimination or survival.
View Article and Find Full Text PDFMptpB Inhibitor Improves the Action of Antibiotics against and Nontuberculous Infections.
ACS Infect Dis
January 2024
School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, M13 9PT Manchester, U.K.
Treatment of and infections requires multiple drugs for long time periods. Mycobacterium protein-tyrosine-phosphatase B (MptpB) is a key virulence factor that subverts host antimicrobial activity to promote intracellular survival. Inhibition of MptpB reduces the infection burden and offers new opportunities to improve current treatments.
View Article and Find Full Text PDFThe rapid construction and biological evaluation of densely substituted pyrrolo[1,2-]indoles a BF·OEt-assisted cascade approach.
Org Biomol Chem
December 2023
Department of Chemistry, Indian Institute of Technology Jodhpur, Jodhpur 342037, Rajasthan, India.
Lewis-acid cascade reactions promoted by BF·OEt are reported for the synthesis of highly substituted pyrrolo[1,2-]indoles and congeners of benzofuro[2,3-]indoles. These reactions are highly regio- and diastereoselective towards generating up to five contiguous stereogenic centers, including two vicinal quaternary centers. Furthermore, an established cascade approach and the mechanism proposed herein are well supported by quantum chemistry calculations.
View Article and Find Full Text PDFDesign, synthesis and biological evaluation of 3-substituted-2-thioxothiazolidin-4-one (rhodanine) derivatives as antitubercular agents against Mycobacterium tuberculosis protein tyrosine phosphatase B.
Eur J Med Chem
October 2023
Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Chinese Academy of Medical Sciences Key Laboratory of Anti-DR TB Innovative Drug Research, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing, 100050, PR China. Electronic address:
Mycobacterium tuberculosis infections still pose a serious threat to human health. Combination therapies are effective medical solutions to the problem. Mycobacterium tuberculosis is an intracellular pathogen that mainly depends on a virulence factor (Mycobacterium tuberculosis protein tyrosine phosphatase B, MptpB) for its survival in the host.
View Article and Find Full Text PDFAn Insight into MptpB Inhibitors as a Key Strategy to Treat MDR and XDRTuberculosis.
Curr Pharm Des
May 2023
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Raebareli, New Transit Campus, Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow, Uttar Pradesh, 226002, India.
Tuberculosis (TB) is a chronic, air-borne infectious disease caused by Mycobacterium tuberculosis (Mtb), which prominently affects the lungs and usually manifests in other organs. TB is preventable and curable but what makes it challenging is the emergence of resistance to the available treatment options. MDR-continued TB's expansion is one of the world's most pressing and difficult problems.
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!