Unser 10. Leibniz Plant Biochemistry Symposium am 7. und 8. Mai war ein großer Erfolg. Thematisch ging es in diesem Jahr um neue Methoden und Forschungsansätze der Naturstoffchemie. Die exzellenten Vorträge über Wirkstoffe…
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…
Edeler, D.; Bensing, C.; Schmidt, H.; Kaluđerović, G. N.;Preparation and in vitro investigations of triphenyl[ω-(tetrahydro-2H-pyran-2-yloxy)alkyl]tin(IV) compoundsAppl. Organomet. Chem.31e3630(2017)DOI: 10.1002/aoc.3630
The reaction of SnPh3Li with X(CH2)nO–THP (THP = tetrahydro‐2H‐pyran‐2‐yl; n = 3, 4, 6, 8, 11; X = Cl, Br) afforded organotin(IV) compounds with the general formula Ph3Sn(CH2)nO–THP (1–5). The tetraorganotin(IV) compounds were characterized using multinuclear NMR and infrared spectroscopies and high‐resolution mass spectrometry. Anticancer activity of the synthesized compounds was tested in vitro against the A2780 (ovarian), A549 (lung), HeLa (adenocarcinoma) and SW480 (colon) tumour cell lines with SRB assay. The in vitro investigations revealed that when a shorter chain was present a higher activity was achieved; however compounds 1–5 were found to be less active than cisplatin. In addition, the most active compound, 1, enters A2780 cells and causes apoptosis by triggering both intrinsic and extrinsic caspase pathways.
Publikation
Wiemann, J.; Karasch, J.; Loesche, A.; Heller, L.; Brandt, W.; Csuk, R.;Piperlongumine B and analogs are promising and selective inhibitors for acetylcholinesteraseEur. J. Med. Chem.139222-231(2017)DOI: 10.1016/j.ejmech.2017.07.081
Piperlongumine B (19), an alkaloid previously isolated from long pepper (Piper longum) has been synthesized for the first time in a short sequence and in good yield together with 19 analogs. Screening of these compounds in Ellman's assays showed several of them to be good inhibitors of acetylcholinesterase while being less active for butyrylcholinesterase. Activity of the compounds increased with the ring size of the heterocycle, and a maximum of activity was observed for an analog holding 12 methylene groups in the aliphatic side chain. These compounds may be regarded as promising candidates for the development of efficient inhibitors of acetylcholinesterase being useful for the treatment of Alzheimer's disease.
Publikation
Heller, L.; Kahnt, M.; Loesche, A.; Grabandt, P.; Schwarz, S.; Brandt, W.; Csuk, R.;Amino derivatives of platanic acid act as selective and potent inhibitors of butyrylcholinesteraseEur. J. Med. Chem.126652-668(2017)DOI: 10.1016/j.ejmech.2016.11.056
A set of thirtyfive 30-norlupan derivatives (2–36) was prepared from the natural triterpenoid platanic acid (PA), and the hydroxyl group at C-3, the carboxyl group at C-17 and the carbonyl group at C-20 were modified. These derivatives were tested for their inhibitory activity for the enzymes acetylcholinesterase (AChE, from electric eel) and butyrylcholinesterase (BChE, from equine serum) using Ellman's assay. Extra enzyme kinetic studies were performed. The most active compound was (3β, 20R)-3-acetyloxy-20-amino-30-norlupan-28-oate (32) showing a Ki value of 0.01 ± 0.003 μM for BChE. This compound proved to be a selective (FB = 851), mixed-type inhibitor for BChE.
Publikation
Loesche, A.; Wiese, J.; Sommerwerk, S.; Simon, V.; Brandt, W.; Csuk, R.;Repurposing N,N'-bis-(arylamidino)-1,4-piperazinedicarboxamidines: An unexpected class of potent inhibitors of cholinesterasesEur. J. Med. Chem.125430-434(2017)DOI: 10.1016/j.ejmech.2016.09.051
Drug repurposing (=drug repositioning) is an effective way to cut costs for the development of new therapeutics and to reduce the time-to-market time-span. Following this concept a small library of compounds was screened for their ability to act as inhibitors of acetyl- and butyrylcholinesterase. Picloxydine, an established antiseptic, was shown to be an inhibitor for both enzymes. Systematic variation of the aryl substituents led to analogs possessing almost the same good properties as gold standard galantamine hydrobromide.