Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Seit Februar 2021 bietet Wolfgang Brandt, ehemaliger Leiter der Arbeitsgruppe Computerchemie am IPB, sein Citizen Science-Projekt zur Pilzbestimmung an. Dafür hat er in regelmäßigen Abständen öffentliche Vorträge zur Vielfalt…
Müllers, Y.; Sadr, A. S.; Schenderlein, M.; Pallab, N.; D. Davari, M.; Glebe, U.; Reifarth, M.;Acrylate‐derived RAFT polymers for enzyme hyperactivation – boosting the α‐chymotrypsin enzyme activity using tailor‐made poly(2‐carboxyethyl)acrylate (PCEA)ChemCatChem16e202301685(2024)DOI: 10.1002/cctc.202301685
We study the hyperactivation of α‐chymotrypsin (α‐ChT) using the acrylate polymer poly(2‐carboxyethyl) acrylate (PCEA) in comparison to the commonly used poly(acrylic acid) (PAA). The polymers are added during the enzymatic cleavage reaction of the substrate N‐glutaryl‐L‐phenylalanine p‐nitroanilide (GPNA). Enzyme activity assays reveal a pronounced enzyme hyperactivation capacity of PCEA, which reaches up to 950% activity enhancement, and is significantly superior to PAA (revealing an activity enhancement of approx. 450%). In a combined experimental and computational study, we investigate α‐ChT/polymer interactions to elucidate the hyperactivation mechanism of the enzyme. Isothermal titration calorimetry reveals a pronounced complexation between the polymer and the enzyme. Docking simulations reveal that binding of polymers significantly improves the binding affinity of GPNA to α‐ChT. Notably, a higher binding affinity is found for the α‐ChT/PCEA compared to the α‐ChT/PAA complex. Further molecular dynamics (MD) simulations reveal changes in the size of the active site in the enzyme/polymer complexes, with PCEA inducing a more pronounced alteration compared to PAA, facilitating an easier access for the substrate to the active site of α‐ChT.
Publikation
Smolková, R.; Smolko, L.; Samoľová, E.; Morgan, I.; Rennert, R.; Kaluđerović, G. N.;Novel Zn(ii), Co(ii) and Cu(ii) diflunisalato complexes with neocuproine and their exceptional antiproliferative activity against cancer cell linesDalton Trans.5317595-17607(2024)DOI: 10.1039/d4dt01736f
Three novel complexes of deprotonated diflunisal (dif) with neocuproine (neo) were synthesized and characterized via elemental, spectral (UV-vis, FTIR, fluorescence, and mass spectrometry), and single-crystal X-ray diffraction analyses. Although the compounds shared a similar composition of [MCl(dif)(neo)], where M represents Zn(II) (1), Co(II) (2) and Cu(II) (3), only 1 and 2 were isostructural, while 3 differed in both the molecular and supramolecular structures. In all three complex molecules, the central atom is coordinated by two nitrogen atoms of neo in a bidentate chelate mode, and one chlorido ligand and dif is bonded in either a monodentate mode via one oxygen atom of the carboxylate in 1 and 2 or in a bidentate chelate mode via both carboxylate oxygen atoms in 3. All three compounds demonstrated remarkable antiproliferative activity against human prostate (PC-3), colon (HCT116) and breast (MDA-MB-468) cancer cell lines with IC50 values in the nanomolar range, with the lowest values observed in the case of PC-3 and MDA-MB-468 with 2 (20.0 nM) and 3 (31.1 nM), respectively. Moreover, complex 2, as the most active, was further investigated for its potential to induce perturbations in the cell cycle of PC-3 cells. The results indicated an induction of caspase-independent apoptosis. The interaction of the complexes with genomic DNA isolated from the respective cancer cell lines was evaluated for the intercalative mode, with binding strength correlated with the antiproliferative activity against PC-3 and MDA-MB-468 cancer cell lines.
Publikation
Predarska, I.; Saoud, M.; Morgan, I.; Eichhorn, T.; Kaluđerović, G. N.; Hey-Hawkins, E.;Cisplatin−cyclooxygenase inhibitor conjugates, free and immobilised in mesoporous silica SBA-15, prove highly potent against triple-negative MDA-MB-468 breast cancer cell lineDalton Trans.51857–869(2022)DOI: 10.1039/d1dt03265h
For the development of anticancer drugs with higher activity and reduced
toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II)
counterparts and loading them into mesoporous silica SBA-15 with the
aim to utilise the passive enhanced permeability and retention (EPR)
effect of nanoparticles for accumulation in tumour tissues. Three
conjugates based on a cisplatin scaffold bearing the anti-inflammatory
drugs naproxen, ibuprofen or flurbiprofen in the axial positions (1, 2 and 3, respectively) were synthesised and loaded into SBA-15 to afford the mesoporous silica nanoparticles (MSNs) SBA-15|1, SBA-15|2 and SBA-15|3.
Superior antiproliferative activity of both free and immobilised
conjugates in a panel of four breast cancer cell lines (MDA-MB-468,
HCC1937, MCF-7 and BT-474) with markedly increased cytotoxicity with
respect to cisplatin was demonstrated. All compounds exhibit highest
activity against the triple-negative cell line MDA-MB-468, with
conjugate 1 being the most potent. However, against MCF-7 and BT-474 cell lines, the most notable improvement was found, with IC50
values up to 240-fold lower than cisplatin. Flow cytometry assays
clearly show that all compounds induce apoptotic cell death elevating
the levels of both early and late apoptotic cells. Furthermore,
autophagy as well as formation of reactive oxygen species (ROS) and
nitric oxide (NO) were elevated to a similar or greater extent than with
cisplatin.
Publikation
Mpetga, J. D. S.; Nago, R. D. T.; Tamokou, J.-D.-D.; Fobofou, S. A. T.; Bitchagno, G. T. M.; Wessjohann, L. A.; Tene, M.; Ngouela, A. S.;A new ceramide from Cissus aralioides Baker (Vitaceae) and its antimicrobial activityChem. Biodivers.19e202200678(2022)DOI: 10.1002/cbdv.202200678
Purification through repeated column chromatography over silica gel and Sephadex LH-20 of the ethanol extract of the stems of Cissus aralioides (Baker) Planch. resulted in the isolation of a new ceramide, aralioidamide A (1) along with five known compounds (2-6). Their structures were determined by the extensive analysis of their spectroscopic (1D and 2D NMR) and spectrometric data, and comparison with those reported in the literature. Aralioidamide A (1) displayed weak antibacterial activity (MIC = 256 μg/mL) against Bacillus subtilis, Staphylococcus aureus and Shigella flexneri and was inactive (MIC > 256 μg/mL) against the tested fungi.