A5022362657- Microbial Natural Products and Biosynthesis
- Fungal Biology and Applications
- Synthesis and biological activity
- Quinazolinone synthesis and applications
- Peptidase Inhibition and Analysis
- Essential Oils and Antimicrobial Activity
- Antibiotic Resistance in Bacteria
- Plant Pathogens and Fungal Diseases
- Phenothiazines and Benzothiazines Synthesis and Activities
- Crystallization and Solubility Studies
- Signaling Pathways in Disease
- Cancer therapeutics and mechanisms
- Protein Degradation and Inhibitors
- X-ray Diffraction in Crystallography
- Marine Sponges and Natural Products
- Toxin Mechanisms and Immunotoxins
- Antimicrobial Peptides and Activities
- Plant biochemistry and biosynthesis
- Plant Pathogenic Bacteria Studies
- Psoriasis: Treatment and Pathogenesis
- Traditional and Medicinal Uses of Annonaceae
- Indoor Air Quality and Microbial Exposure
- Cancer Mechanisms and Therapy
- Bacterial biofilms and quorum sensing
- Polymer Surface Interaction Studies
Heinrich Heine University Düsseldorf
2017-2024
The ClpC1:ClpP1P2 protease is a core component of the proteostasis system in mycobacteria. To improve efficacy antitubercular agents targeting Clp protease, we characterized mechanism antibiotics cyclomarin A and ecumicin. Quantitative proteomics revealed that cause massive proteome imbalances, including upregulation two unannotated yet conserved stress response factors, ClpC2 ClpC3. These proteins likely protect from excessive amounts misfolded or A, which show to mimic damaged proteins....
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...
The OSMAC (one strain many compounds) concept is a cultivation-based approach to increase the diversity of secondary metabolites in microorganisms. In this study, we applied OSMAC-approach endophytic fungus Trichocladium sp. by supplementation cultivation medium with 2.5% phenylalanine. This experiment yielded five new compounds, trichocladiol (1), trichocladic acid (2), colletodiolic (3), colletolactone (4) and colletolic (5), together previously described ones (6-10). structures were...
Abstract Tuberculosis-causing Mycobacterium tuberculosis (Mtb) is transmitted via airborne droplets followed by a primary infection of macrophages and dendritic cells. During the activation host defence mechanisms also neutrophils T helper 1 (T H 1) 17 cells are recruited to site infection. The cell-derived interleukin (IL)-17 in turn induces cathelicidin LL37 which shows direct antimycobacterial effects. Here, we investigated role IL-26, 1- 17-associated cytokine that exhibits antimicrobial...
In the quest for new antibacterial lead structures, activity screening against
Abstract Due to a high unresponsiveness chemotherapy, biofilm formation is an important medical problem that frequently occurs during infection with many bacterial pathogens. In this study, the marine sponge-derived natural compounds 4,6-dibromo-2-(2′,4′-dibromophenoxy)phenol and 3,4,6-tribromo-2-(2′,4′-dibromophenoxy)phenol were found exhibit broad antibacterial activity against medically relevant gram-positive gram-negative The not only bactericidal both replicating stationary...
Toxoplasma gondii is an apicomplexan pathogen able to infect a wide range of warm-blooded animals, including humans, leading toxoplasmosis. Current treatments for toxoplasmosis are associated with severe side-effects and lack efficacy eradicate chronic infection. Thus, there urgent need developing novel, highly efficient agents against low toxicity. For decades, natural products have been useful source novel bioactive compounds the treatment infectious pathogens. In present study, we...
Clonostachys rosea is a fungus widely distributed on Earth and has high capacity to adapt complex environments in soil, plants, or sea. It an endophyte that can be used as potential biocontrol agent protect plants from pathogenic fungi, nematodes, insects. However, the spectrum of secondary metabolites produced by C. only scarcely been studied. In present study, eight new phenalenones, asperphenalenones F-M (1-8), together with two known derivatives, E B (9 10), were isolated axenic rice...
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....
Extremophilic fungi have received considerable attention recently as new promising sources of biologically active compounds with potential pharmaceutical applications. This study investigated the secondary metabolites a marine-derived Penicillium ochrochloron isolated from underwater sea sand collected North Sea in St. Peter-Ording, Germany. Standard techniques were used for fungal isolation, taxonomic identification, fermentation, extraction, and isolation metabolites. Chromatographic...
Chemical investigation of the ethyl acetate extract fungus Acremonium sp., derived from inner tissue anise roots, led to isolation and characterization one new chlorinated compound, acremochlorin O ( 1 ), together with five related derivatives 2 – 6 ) an alkaloidal metabolite, ilicicolin H 7 ). Structure elucidation isolated compounds was determined based on extensive 1D/2D NMR spectroscopic analyses HR-ESI-MS measurements. The absolute configuration established using electronic circular...
Abstract A new series of 4-nitroimidazole bearing aryl piperazines 7–16 , tetrazole 17 and 1,3,4-thiadiazole 18 derivatives was synthesized. All were screened for their anticancer activity against eight diverse human cancer cell lines (Capan-1, HCT-116, LN229, NCI–H460, DND-41, HL-60, K562, Z138). Compound proved the most potent compound inhibiting proliferation selected with IC 50 values in low micromolar range. In addition, 11 exhibited ranging 8.60–64.0 μM a selection lines. These...
ABSTRACT Tuberculosis (TB), a significant cause of mortality globally, continues to claim 1.5 million lives each year. Despite recent advances in TB management, the emergence multidrug-resistant strains is exacerbating treatment TB. Therefore, there an immediate necessity uncover new anti-TB compounds with unprecedented targets. This study introduces novel antimycobacterial molecules that are based on α-aminooxyacetic acid core structures. The lead KSK-104 and KSK-106 displayed potent...
In this study, a library of 3,7-di(hetero)aryl-substituted 10-(3-trimethylammoniumpropyl)10H-phenothiazine salts is prepared. These title compounds and their precursors are reversible redox systems with tunable potentials. The Hammett correlation gives very good the first oxidation potentials σp parameters. Furthermore, blue to green-blue emissive. Screening reveals for some derivatives distinct inhibition several pathogenic bacterial strains (Mycobacterium tuberculosis, Staphylococcus...
Three sulfur-containing alkaloids aplospojaveedins A–C (1–3) with a hitherto undescribed carbon skeleton comprising octahy-dronaphthalene, α , β -unsaturated lactam and glycine-cysteine moieties were isolated from Aplosporella javeedii . Their structures elucidated by 1D 2D NMR spectroscopy, HR-MS, X-ray diffraction analysis, DFT-NMR TDDFT-ECD calculations. A plausible biosynthetic pathway putative targets are described. The blind docking suggested that 1–3 may have functional effects on...
<title>Abstract</title> A new series of 4-nitroimidazole bearing substituted aryl piperazines <bold>7</bold>-<bold>16</bold>, tetrazole <bold>17</bold> and 1,3,4-thiadiazole <bold>18</bold> derivatives was designed synthesized. All were screened for their anticancer activity against eight diverse human cancer cell lines (Capan-1, HCT-116, LN229, NCI-H460, DND-41, HL-60, K562 Z138). Compound proved the most potent compound inhibiting proliferation selected with IC<sub>50</sub> values in low...