Omanische Heilpflanze im Fokus der Phytochemie IPB-Wissenschaftler und Partner aus Dhofar haben jüngst die omanische Heilpflanze Terminalia dhofarica unter die phytochemische Lupe genommen. Die Pflanze ist reich an…
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…
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
Humpierre, A. R.; Zanuy, A.; Saenz, M.; Vasco, A. V.; Méndez, Y.; Westermann, B.; Cardoso, F.; Quintero, L.; Santana, D.; Verez, V.; Valdés, Y.; Rivera, D. G.; Garrido, R.;Quantitative NMR for the structural analysis of novel bivalent glycoconjugates as vaccine candidatesJ. Pharm. Biomed. Anal.214114721(2022)DOI: 10.1016/j.jpba.2022.114721
Novel unimolecular bivalent glycoconjugates were assembled combining several functionalized capsular polysaccharides of Streptococcus pneumoniae and Neisseria meningitidis to a carrier protein by using an effective strategy based on the Ugi 4-component reaction. The development of multivalent glycoconjugates opens new opportunities in the field of vaccine design, but their high structural complexity involves new analytical challenges. Nuclear Magnetic Resonance has found wide applications in the characterization and impurity profiling of carbohydrate-based vaccines. Eight bivalent conjugates were studied by quantitative NMR analyzing the structural identity, the content of each capsular polysaccharide, the ratios between polysaccharides, the polysaccharide to protein ratios and undesirable contaminants. The qNMR technique involves experiments with several modified parameters for obtaining spectra with quantifiable signals. In addition, the achieved NMR results were combined with the results of colorimetric assay and Size Exclusion HPLC for assessing the protein content and free protein percentage, respectively. The application of quantitative NMR showed to be efficient to clear up the new structural complexities while allowing the quantitative assessment of the components.
Publikation
Farag, M. A.; Shakour, Z. T.; Lübken, T.; Frolov, A.; Wessjohann, L. A.; Mahrous, E.;Unraveling the metabolome composition and its implication for Salvadora persica L. use as dental brush via a multiplex approach of NMR and LC–MS metabolomicsJ. Pharm. Biomed. Anal.193113727(2021)DOI: 10.1016/j.jpba.2020.113727
Salvadora persica L. (toothbrush tree, Miswak) is well recognized in most Middle Eastern and African countries for its potential role in dental care, albeit the underlying mechanism for its effectiveness is still not fully understood. A comparative MS and NMR metabolomics approach was employed to investigate the major primary and secondary metabolites composition of S. persica in context of its organ type viz., root or stem to rationalize for its use as a tooth brush. NMR metabolomics revealed its enrichment in nitrogenous compounds including proline-betaines i.e., 4-hydroxy-stachydrine and stachydrine reported for the first time in S. persica. LC/MS metabolomics identified flavonoids (8), benzylurea derivatives (5), butanediamides (3), phenolic acids (8) and 5 sulfur compounds, with 21 constituents reported for the first time in S. persica. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) of either NMR or LC/MS dataset clearly separated stem from root specimens based on nitrogenous compounds abundance in roots and is justifying for its preference as toothbrush versus stems. The presence of betaines at high levels in S. persica (9−12 μg/mg dry weight) offers novel insights into its functioning as an osmoprotectant that maintains the hydration of oral mucosa. Additionally, the previously described anti-inflammatory activity of stachydrine along with the antimicrobial effects of sulfonated flavonoids, benzylisothiocynate and ellagic acid derivatives are likely contributors to S. persica oral hygiene health benefits. Among root samples, variation in sugars and organic acids levels were the main discriminatory criterion. This study provides the first standardization of S. persica extract using qNMR for further inclusion in nutraceuticals.