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Verfasst von:Uliassi, Elisa [VerfasserIn]   i
 Krauth-Siegel, Renate [VerfasserIn]   i
Titel:Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity
Verf.angabe:Elisa Uliassi, Giulia Fiorani, R. Luise Krauth-Siegel, Christian Bergamini, Romana Fato, Giulia Bianchini, J. Carlos Menéndez, Maria Teresa Molina, Eulogio López-Montero, Federico Falchi, Andrea Cavalli, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Gesa Witt, Carolina B. Moraes, Lucio H. Freitas-Junior, Chiara Borsari, Maria Paola Costi, Maria Laura Bolognesi
E-Jahr:2017
Jahr:3 October 2017
Umfang:11 S.
Fussnoten:Gesehen am 01.10.2018
Titel Quelle:Enthalten in: European journal of medicinal chemistry
Ort Quelle:Amsterdam [u.a.] : Elsevier Science, 1987
Jahr Quelle:2017
Band/Heft Quelle:141(2017), Seite 138-148
ISSN Quelle:1768-3254
Abstract:Crassiflorone is a natural product with anti-mycobacterial and anti-gonorrhoeal properties, isolated from the stem bark of the African ebony tree Diospyros crassiflora. We noticed that its pentacyclic core possesses structural resemblance to the quinone-coumarin hybrid 3, which we reported to exhibit a dual-targeted inhibitory profile towards Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR). Following this basic idea, we synthesized a small library of crassiflorone derivatives 15-23 and investigated their potential as anti-trypanosomatid agents. 19 is the only compound of the series showing a balanced dual profile at 10 μM (% inhibitionTbGAPDH = 64% and % inhibitionTcTR = 65%). In phenotypic assay, the most active compounds were 18 and 21, which at 5 μM inhibited Tb bloodstream-form growth by 29% and 38%, respectively. Notably, all the newly synthesized compounds at 10 μM did not affect viability and the status of mitochondria in human A549 and 786-O cell lines, respectively. However, further optimization that addresses metabolic liabilities including solubility, as well as cytochromes P450 (CYP1A2, CYP2C9, CYP2C19, and CYP2D6) inhibition, is required before this class of natural product-derived compounds can be further progressed.
DOI:doi:10.1016/j.ejmech.2017.10.005
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: http://dx.doi.org/10.1016/j.ejmech.2017.10.005
 Volltext: http://www.sciencedirect.com/science/article/pii/S0223523417307973
 DOI: https://doi.org/10.1016/j.ejmech.2017.10.005
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Coumarins
 Crassiflorone
 Glyceraldehyde-3-phosphate dehydrogenase
 Leishmaniasis
 Natural products
 Quinones
 Trypanocidal activity
 Trypanosomiasis
 Trypanothione reductase
K10plus-PPN:1581457626
Verknüpfungen:→ Zeitschrift

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