Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity
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 exhibi...
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
3 October 2017
|
| In: |
European journal of medicinal chemistry
Year: 2017, Jahrgang: 141, Pages: 138-148 |
| ISSN: | 1768-3254 |
| DOI: | 10.1016/j.ejmech.2017.10.005 |
| Online-Zugang: | Verlag, Pay-per-use, Volltext: http://dx.doi.org/10.1016/j.ejmech.2017.10.005 Verlag, Pay-per-use, Volltext: http://www.sciencedirect.com/science/article/pii/S0223523417307973 
|
| Verfasserangaben: | 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1581457626 | ||
| 003 | DE-627 | ||
| 005 | 20240316100528.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 181001s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.ejmech.2017.10.005 |2 doi | |
| 035 | |a (DE-627)1581457626 | ||
| 035 | |a (DE-576)511457626 | ||
| 035 | |a (DE-599)BSZ511457626 | ||
| 035 | |a (OCoLC)1341019261 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 30 |2 sdnb | ||
| 100 | 1 | |a Uliassi, Elisa |e VerfasserIn |0 (DE-588)1168186641 |0 (DE-627)1031824987 |0 (DE-576)511458150 |4 aut | |
| 245 | 1 | 0 | |a Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity |c 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 |
| 264 | 1 | |c 3 October 2017 | |
| 300 | |a 11 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 01.10.2018 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Coumarins | |
| 650 | 4 | |a Crassiflorone | |
| 650 | 4 | |a Glyceraldehyde-3-phosphate dehydrogenase | |
| 650 | 4 | |a Leishmaniasis | |
| 650 | 4 | |a Natural products | |
| 650 | 4 | |a Quinones | |
| 650 | 4 | |a Trypanocidal activity | |
| 650 | 4 | |a Trypanosomiasis | |
| 650 | 4 | |a Trypanothione reductase | |
| 700 | 1 | |a Krauth-Siegel, Renate |e VerfasserIn |0 (DE-588)1050022335 |0 (DE-627)783217390 |0 (DE-576)404300200 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t European journal of medicinal chemistry |d Amsterdam [u.a.] : Elsevier Science, 1987 |g 141(2017), Seite 138-148 |h Online-Ressource |w (DE-627)320443213 |w (DE-600)2005170-0 |w (DE-576)25927125X |x 1768-3254 |7 nnas |a Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity |
| 773 | 1 | 8 | |g volume:141 |g year:2017 |g pages:138-148 |g extent:11 |a Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.ejmech.2017.10.005 |x Verlag |x Resolving-System |z Pay-per-use |3 Volltext |
| 856 | 4 | 0 | |u http://www.sciencedirect.com/science/article/pii/S0223523417307973 |x Verlag |z Pay-per-use |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20181001 | ||
| 993 | |a Article | ||
| 994 | |a 2017 | ||
| 998 | |g 1050022335 |a Krauth-Siegel, Renate |m 1050022335:Krauth-Siegel, Renate |d 700000 |d 711000 |e 700000PK1050022335 |e 711000PK1050022335 |k 0/700000/ |k 1/700000/711000/ |p 3 | ||
| 999 | |a KXP-PPN1581457626 |e 3027493787 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"recId":"1581457626","language":["eng"],"note":["Gesehen am 01.10.2018"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"person":[{"family":"Uliassi","given":"Elisa","roleDisplay":"VerfasserIn","display":"Uliassi, Elisa","role":"aut"},{"given":"Renate","family":"Krauth-Siegel","role":"aut","display":"Krauth-Siegel, Renate","roleDisplay":"VerfasserIn"}],"title":[{"title_sort":"Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity","title":"Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activity"}],"relHost":[{"type":{"media":"Online-Ressource","bibl":"periodical"},"note":["Gesehen am 22.11.04"],"disp":"Crassiflorone derivatives that inhibit Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR) and display trypanocidal activityEuropean journal of medicinal chemistry","language":["eng"],"recId":"320443213","pubHistory":["Nachgewiesen 22.1987 -"],"part":{"year":"2017","pages":"138-148","volume":"141","text":"141(2017), Seite 138-148","extent":"11"},"title":[{"title_sort":"European journal of medicinal chemistry","title":"European journal of medicinal chemistry"}],"physDesc":[{"extent":"Online-Ressource"}],"origin":[{"dateIssuedKey":"1987","publisher":"Elsevier Science","dateIssuedDisp":"1987-","publisherPlace":"Amsterdam [u.a.]"}],"id":{"zdb":["2005170-0"],"eki":["320443213"],"issn":["1768-3254"]}}],"physDesc":[{"extent":"11 S."}],"name":{"displayForm":["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"]},"id":{"doi":["10.1016/j.ejmech.2017.10.005"],"eki":["1581457626"]},"origin":[{"dateIssuedKey":"2017","dateIssuedDisp":"3 October 2017"}]} | ||
| SRT | |a ULIASSIELICRASSIFLOR3201 | ||