A5074243457- Microbial Natural Products and Biosynthesis
- Signaling Pathways in Disease
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Tuberculosis Research and Epidemiology
- Pharmacological Effects of Natural Compounds
- Essential Oils and Antimicrobial Activity
- Phytochemistry and Biological Activities
- Alkaloids: synthesis and pharmacology
- Antimicrobial Peptides and Activities
- Plant biochemistry and biosynthesis
- Insect Pest Control Strategies
- Enzyme function and inhibition
- Cancer therapeutics and mechanisms
- Cancer Mechanisms and Therapy
Heinrich Heine University Düsseldorf
2023-2024
Abstract Antimicrobial resistance is a global health threat that requires the development of new treatment concepts. These should not only overcome existing but be designed to slow down emergence mechanisms. Targeted protein degradation, whereby drug redirects cellular proteolytic machinery towards degrading specific target, an emerging concept in discovery. We are extending this by developing proteolysis targeting chimeras active bacteria (BacPROTACs) bind ClpC1, component mycobacterial...
About 100,000 deaths are attributed annually to infections with methicillin-resistant Staphylococcus aureus (MRSA) despite concerted efforts toward vaccine development and clinical trials involving several preclinically efficacious drug candidates. This necessitates the of alternative therapeutic options against this drug-resistant bacterial pathogen. Using Masuda borylation-Suzuki coupling (MBSC) sequence, we previously synthesized modified naturally occurring bisindole alkaloids, alocasin...
Antimicrobial resistance is a global health threat that requires development of new treatment concepts. These should not only overcome existing resistance, but be designed to slow down emergence mechanisms. Targeted protein degradation, whereby drug redirects cellular proteolytic machinery towards degrading specific target, an emerging concept in discovery. We developed proteolysis targeting chimeras active bacteria (BacPROTACs) bind ClpC1, component the mycobacterial degradation machinery....
Spread of antimicrobial resistances urges a need for new drugs against Mycobacterium tuberculosis (Mtb) with mechanisms differing from current antibiotics. Previously, callyaerins were identified as promising anti-tubercular agents, representing class hydrophobic cyclopeptides an unusual (Z)-2,3-di-aminoacrylamide unit. Here, we investigated the molecular underlying their antimycobacterial properties. Structure-activity relationship studies enabled identification structural determinants...
Multidrug-resistant pathogens pose a major threat to human health, necessitating the identification of new drug targets and lead compounds that are not susceptible cross-resistance. This study demonstrates novel reverse thia analogs phosphonohydroxamic acid antibiotic fosmidomycin inhibit 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme for Plasmodium falciparum, Escherichia coli, Mycobacterium tuberculosis is absent in humans. Some with large α-phenyl substituents...
ABSTRACT Spread of antimicrobial resistances in the pathogen Mycobacterium tuberculosis remains a public health challenge. Thus, there is continuous need for new therapeutic options with modes-of-action differing from current antibiotics. Previously, bioactivity-guided isolation identified callyaerins, class hydrophobic cyclopeptides an unusual ( Z )-2,3-di-aminoacrylamide unit, as promising antitubercular agents. In this study, we investigated molecular mechanisms underlying their...