A5064230603- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Histone Deacetylase Inhibitors Research
- Adenosine and Purinergic Signaling
- Microbial Natural Products and Biosynthesis
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Receptor Mechanisms and Signaling
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Fungal Biology and Applications
- Neuropeptides and Animal Physiology
- Metal complexes synthesis and properties
- Calcium signaling and nucleotide metabolism
- Marine Sponges and Natural Products
- Diabetes Treatment and Management
- Crystallography and molecular interactions
- Cancer therapeutics and mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic function and diabetes
- Bioactive Compounds and Antitumor Agents
- Pharmacological Receptor Mechanisms and Effects
- Synthesis and pharmacology of benzodiazepine derivatives
- Drug Transport and Resistance Mechanisms
- Growth Hormone and Insulin-like Growth Factors
Heinrich Heine University Düsseldorf
2016-2025
University of Groningen
2017
University of Debrecen
2014
Martin Luther University Halle-Wittenberg
2012
RWTH Aachen University
2005-2012
Central Drug Research Institute
2009
University of Bonn
1998-2008
University of Southern Denmark
2008
University of Hawaii at Hilo
2007
Friedrich Schiller University Jena
2002-2005
In this work, we synthesized a series of peptoid-based histone deacetylase (HDAC) inhibitors with variations in the linker region and zinc-binding groups. All compounds were investigated for their HDAC inhibition, antiplasmodial activity, cytotoxicity against native cisplatin-resistant carcinoma cell lines. The ethylhydrazide 20 (DS-103) proved to be most effective compound these primary screenings. DS-103 showed nanomolar inhibition class I HDACs HDAC6 (class IIb). To further investigate...
Cell viability assays are important tools in oncological research and clinical practice to assess the tumor cell sensitivity of individual patients. The purpose this study was demonstrate comparability 3 widely used (MTT, ATP, calcein assays) by principal component analysis. included 4 different cytostatics (cisplatin, docetaxel, doxorubicin, vinblastine) human cancer lines (MCF-7, A2780, doxorubicin resistant A2780adr). Ninety-three percent total variance all variables analysis (resulting...
Suramin is a symmetric polyanionic naphthylurea originally used for the treatment of trypanosomiasis and onchocerciasis. diverse analogues exhibit broad range biological actions in vitro vivo, including, among others, antiproliferative antiviral activity. derivatives usually target purinergic binding sites. Class III histone deacetylases (sirtuins) are amidohydrolases that require nicotinamide adenine dinucleotide (NAD(+)) as cofactor their catalytic mechanism(.) Deacetylation proteins leads...
The synthesis and biological evaluation of new potent hydroxamate-based HDAC inhibitors with a novel alkoxyamide connecting unit linker region are described. Biological includes MTT cellular assays on sensitive chemoresistant cancer cell lines as well profiling selected compounds. Compound 19i (LMK235) (N-((6-(hydroxyamino)-6-oxohexyl)oxy)-3,5-dimethylbenzamide) showed similar effects compared to vorinostat inhibition HDACs in pan-HDAC assay but enhanced cytotoxic against the human A2780,...
Platinum plays a central role in the therapy of ovarian cancer, and emergence platinum resistance is major obstacle for clinical management disease. We treated A2780 cancer cells by weekly cycles cisplatin over period 6 months unveiled that enhanced insulin-like growth factor I receptor (IGF-IR) expression autocrine IGF-I are associated with hyperactivation IGF-IR phosphatidylinositol-3-OH kinase (PI3K) pathways cisplatin-resistant cells. levels increased during treatment correlated...
Four new diketopiperazines including spirobrocazines A–C (1–3) and brocazine G (4) were characterized from the mangrove-derived Penicillium brocae MA-231. Compounds 1 2 had a 6/5/6/5/6 cyclic system with rare spirocyclic center at C-2. Their structures absolute configurations determined by spectroscopic analysis, TDDFT-ECD calculations, X-ray diffraction. Compound 4 exhibited potent cytotoxicity against both sensitive cisplatin-resistant human ovarian cancer cells strong antimicrobial...
A series of 4-phenethynyldihydrocinnamic acid agonists the free fatty receptor 1 (FFA1) has been discovered and explored. The preferred compound 20 (TUG-424, EC50 = 32 nM) significantly increased glucose-stimulated insulin secretion at 100 nM may serve to explore role FFA1 in metabolic diseases such as diabetes or obesity.
Neutrophils undergo rapid constitutive apoptosis that is delayed by a range of pathogen- and host-derived inflammatory mediators. We have investigated the ability nucleotide ATP, to which neutrophils are exposed both in circulation at sites inflammation, modulate lifespan human neutrophils. found physiologically relevant concentrations ATP cause concentration-dependent delay neutrophil (assessed morphology, annexin V/To-Pro3 staining, mitochondrial membrane permeabilization). even brief...
Four tetrahydroxanthone dimers (1-4) and four biogenetically related monomers (5-8), including the new derivatives 4-6, were isolated from endophyte Phomopsis longicolla. The absolute configurations of 2-4 established for first time by TDDFT electronic circular dichroism calculations, that phomoxanthone A (1) was revised X-ray crystallography. Phomoxanthone showed strongest pro-apoptotic activity when tested against a panel human cancer cell lines, cisplatin-resistant cells, whereas it up to...
Purpose.Several studies have shown that natural compounds like resveratrol or ellagic acid anticancer and antioxidant properties can stimulate apoptosis in many cancer cell lines.The aim of this study was to elucidate if acid, respectively, could improve the efficacy cisplatin ovarian cancer.Methods.As a cellular resistance model, epithelial line A2780 its cisplatin-resistant subclone A2780CisR were used.A2780CisR obtained by intermittent treatment with for 26 weekly cycles showed 4-6-fold...
Seven new 14-membered macrolides, pestalotioprolides C (2), D–H (4–8), and 7-O-methylnigrosporolide (3), together with four known analogues, pestalotioprolide B (1), seiricuprolide (9), nigrosporolide (10), 4,7-dihydroxy-13-tetradeca-2,5,8-trienolide (11), were isolated from the mangrove-derived endophytic fungus Pestalotiopsis microspora. Their structures elucidated by analysis of NMR MS data comparison literature data. Single-crystal X-ray diffraction was used to confirm absolute...
Widely established targeted therapies directed at triple negative breast cancer (TNBC) are missing. Classical chemotherapy remains the systemic treatment option. Cisplatin has been tested in TNBC but bears disadvantage of resistance development. The purpose this study was to identify mechanisms cisplatin-resistant cell lines and select based on these findings.The HCC38 MDA-MB231 were subjected intermittent cisplatin resulting 3.5-fold subclone HCC38CisR 2.1-fold more resistant MDA-MB231CisR....
Histone deacetylase inhibitors (HDACi) are promising anti-cancer drugs that could also be employed for urothelial carcinoma (UC) therapy. It is unclear, however, whether inhibition of all 11 zinc-dependent HDACs or individual enzymes more efficacious and specific. Here, we investigated the novel HDACi 19i (LMK235) with presumed preferential activity against class IIA HDAC4/5 in comparison to pan-HDACi vorinostat (SAHA) HDAC4-specific TMP269 UC cell lines basal expression HDAC4 characterized...
Five new polyhydroxylated hydroanthraquinone derivatives, namely, 8-hydroxyconiothyrinone B (1), 8,11-dihydroxyconiothyrinone (2), 4R,8-dihydroxyconiothyrinone (3), 4S,8-dihydroxyconiothyrinone (4), and 4S,8-dihydroxy-10-O-methyldendryol E (5), were isolated identified from the culture extract of Talaromyces islandicus EN-501, an endophytic fungus obtained inner tissue marine red alga Laurencia okamurai. The structures these compounds established on basis detailed interpretation their NMR...
A chemical investigation of the endophyte Penicillium sp. (strain ZO-R1-1), isolated from roots medicinal plant Zingiber officinale, yielded nine new indole diterpenoids (1–9), together with 13 known congeners (10–22). The structures compounds were elucidated by 1D and 2D NMR analysis in combination HRESIMS data. absolute configuration natural products 1, 3, 7 was determined using TDDFT-ECD approach confirmed for 1 single-crystal X-ray determination through anomalous dispersion. tested...
Inhibition of more than one cancer-related pathway by multi-target agents is an emerging approach in modern anticancer drug discovery. Here, based on the well-established synergy between histone deacetylase inhibitors (HDACi) and alkylating agents, we present discovery a series HDACi using pharmacophore-linking strategy. For parallel synthesis target compounds, developed efficient solid-phase-supported protocol hydroxamic acids immobilized resins (HAIRs) as stable versatile building blocks...