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...
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todo:paper_02235234_v66_n_p355_Leverrier2023-10-03T15:11:16Z Antiparasitic hybrids of Cinchona alkaloids and bile acids Leverrier, A. Bero, J. Frédérich, M. Quetin-Leclercq, J. Palermo, J. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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 Leverrier, A. Bero, J. Frédérich, M. Quetin-Leclercq, J. Palermo, J. 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. |
| format |
JOUR |
| author |
Leverrier, A. Bero, J. Frédérich, M. Quetin-Leclercq, J. Palermo, J. |
| author_facet |
Leverrier, A. Bero, J. Frédérich, M. Quetin-Leclercq, J. Palermo, J. |
| author_sort |
Leverrier, A. |
| 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 |
| url |
http://hdl.handle.net/20.500.12110/paper_02235234_v66_n_p355_Leverrier |
| work_keys_str_mv |
AT leverriera antiparasitichybridsofcinchonaalkaloidsandbileacids AT beroj antiparasitichybridsofcinchonaalkaloidsandbileacids AT frederichm antiparasitichybridsofcinchonaalkaloidsandbileacids AT quetinleclercqj antiparasitichybridsofcinchonaalkaloidsandbileacids AT palermoj antiparasitichybridsofcinchonaalkaloidsandbileacids |
| _version_ |
1782031030874537984 |