Antiparasitic hybrids of Cinchona alkaloids and bile acids
A series of 16 hybrids of Cinchona alkaloids and bile acids (4a-h, 5a-h) was prepared by means of a Barton-Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The ne...
Guardado en:
Autor principal: | |
---|---|
Publicado: |
2013
|
Materias: | |
Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v66_n_p355_Leverrier http://hdl.handle.net/20.500.12110/paper_02235234_v66_n_p355_Leverrier |
Aporte de: |
id |
paper:paper_02235234_v66_n_p355_Leverrier |
---|---|
record_format |
dspace |
spelling |
paper:paper_02235234_v66_n_p355_Leverrier2023-06-08T15:21:46Z Antiparasitic hybrids of Cinchona alkaloids and bile acids Palermo, Jorge Alejandro Antiparasitic activity Barton-Zard reaction Bile acids Cinchona alkaloids Hybrids amphotericin B antimalarial agent antitrypanosomal agent artemisinin bile acid camptothecin Cinchona alkaloid cinchonidine cinchonine quinidine quinine suramin antiparasitic agent bile acid Cinchona alkaloid quinoline antiprotozoal activity article controlled study cytotoxicity decarboxylation drug synthesis human human cell IC 50 Leishmania mexicana Plasmodium falciparum proton nuclear magnetic resonance proton transport Trypanosoma brucei antileishmanial activity antiplasmodial activity antitrypanosomal activity Article drug activity drug cytotoxicity drug synthesis IC50 in vitro study nonhuman Plasmodium Trypanosoma brucei brucei A series of 16 hybrids of Cinchona alkaloids and bile acids (4a-h, 5a-h) was prepared by means of a Barton-Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC50 values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC50 ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC50 values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6-15.7. © 2013 Elsevier Masson SAS. All rights reserved. Fil:Palermo, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v66_n_p355_Leverrier http://hdl.handle.net/20.500.12110/paper_02235234_v66_n_p355_Leverrier |
institution |
Universidad de Buenos Aires |
institution_str |
I-28 |
repository_str |
R-134 |
collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
topic |
Antiparasitic activity Barton-Zard reaction Bile acids Cinchona alkaloids Hybrids amphotericin B antimalarial agent antitrypanosomal agent artemisinin bile acid camptothecin Cinchona alkaloid cinchonidine cinchonine quinidine quinine suramin antiparasitic agent bile acid Cinchona alkaloid quinoline antiprotozoal activity article controlled study cytotoxicity decarboxylation drug synthesis human human cell IC 50 Leishmania mexicana Plasmodium falciparum proton nuclear magnetic resonance proton transport Trypanosoma brucei antileishmanial activity antiplasmodial activity antitrypanosomal activity Article drug activity drug cytotoxicity drug synthesis IC50 in vitro study nonhuman Plasmodium Trypanosoma brucei brucei |
spellingShingle |
Antiparasitic activity Barton-Zard reaction Bile acids Cinchona alkaloids Hybrids amphotericin B antimalarial agent antitrypanosomal agent artemisinin bile acid camptothecin Cinchona alkaloid cinchonidine cinchonine quinidine quinine suramin antiparasitic agent bile acid Cinchona alkaloid quinoline antiprotozoal activity article controlled study cytotoxicity decarboxylation drug synthesis human human cell IC 50 Leishmania mexicana Plasmodium falciparum proton nuclear magnetic resonance proton transport Trypanosoma brucei antileishmanial activity antiplasmodial activity antitrypanosomal activity Article drug activity drug cytotoxicity drug synthesis IC50 in vitro study nonhuman Plasmodium Trypanosoma brucei brucei Palermo, Jorge Alejandro Antiparasitic hybrids of Cinchona alkaloids and bile acids |
topic_facet |
Antiparasitic activity Barton-Zard reaction Bile acids Cinchona alkaloids Hybrids amphotericin B antimalarial agent antitrypanosomal agent artemisinin bile acid camptothecin Cinchona alkaloid cinchonidine cinchonine quinidine quinine suramin antiparasitic agent bile acid Cinchona alkaloid quinoline antiprotozoal activity article controlled study cytotoxicity decarboxylation drug synthesis human human cell IC 50 Leishmania mexicana Plasmodium falciparum proton nuclear magnetic resonance proton transport Trypanosoma brucei antileishmanial activity antiplasmodial activity antitrypanosomal activity Article drug activity drug cytotoxicity drug synthesis IC50 in vitro study nonhuman Plasmodium Trypanosoma brucei brucei |
description |
A series of 16 hybrids of Cinchona alkaloids and bile acids (4a-h, 5a-h) was prepared by means of a Barton-Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC50 values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC50 ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC50 values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6-15.7. © 2013 Elsevier Masson SAS. All rights reserved. |
author |
Palermo, Jorge Alejandro |
author_facet |
Palermo, Jorge Alejandro |
author_sort |
Palermo, Jorge Alejandro |
title |
Antiparasitic hybrids of Cinchona alkaloids and bile acids |
title_short |
Antiparasitic hybrids of Cinchona alkaloids and bile acids |
title_full |
Antiparasitic hybrids of Cinchona alkaloids and bile acids |
title_fullStr |
Antiparasitic hybrids of Cinchona alkaloids and bile acids |
title_full_unstemmed |
Antiparasitic hybrids of Cinchona alkaloids and bile acids |
title_sort |
antiparasitic hybrids of cinchona alkaloids and bile acids |
publishDate |
2013 |
url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02235234_v66_n_p355_Leverrier http://hdl.handle.net/20.500.12110/paper_02235234_v66_n_p355_Leverrier |
work_keys_str_mv |
AT palermojorgealejandro antiparasitichybridsofcinchonaalkaloidsandbileacids |
_version_ |
1768543275136843776 |