Selective Activity Against Amastigote Forms of Trypanosoma cruzi and Leishmania infantum of Diastereomeric Dicentrine N-oxides.

Autor: Tristão DC; Center for Natural and Human Sciences, Federal University of ABC, 09210-580, Santo Andre, SP, Brazil., Barbosa H; Center for Natural and Human Sciences, Federal University of ABC, 09210-580, Santo Andre, SP, Brazil., de Castro Levatti EV; Butantan Institute, 1500, 05503-900, São Paulo, SP, Brazil., Andrade BA; Butantan Institute, 1500, 05503-900, São Paulo, SP, Brazil., Romanelli MM; Butantan Institute, 1500, 05503-900, São Paulo, SP, Brazil., Antar GM; Department of Agricultural and Biological Sciences, Federal University of Espirito Santo, 29932-540, São Matheus, ES, Brazil., Tempone AG; Butantan Institute, 1500, 05503-900, São Paulo, SP, Brazil., Lago JHG; Center for Natural and Human Sciences, Federal University of ABC, 09210-580, Santo Andre, SP, Brazil.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Sep; Vol. 21 (9), pp. e202401247. Date of Electronic Publication: 2024 Aug 11.
DOI: 10.1002/cbdv.202401247
Abstrakt: As part of our continuous research for the discovery of bioactive compounds against Trypanosoma cruzi and Leishmania infantum, the alkaloid (6aS)-dicentrine (1) was oxidized to afford (6aS,6S)- (2) and (6aS,6R)- (3) dicentrine-N-oxides. Evaluation of the cytotoxicity against NCTC cells indicated that 2 and 3 are non-toxic (CC 50 >200 μM) whereas 1 demonstrated CC 50 of 52.0 μM. Concerning T. cruzi activity against amastigotes, derivatives 2 and 3 exhibited EC 50 values of 9.9 μM (SI>20.2) and 27.5 μM (SI>7.3), respectively, but 1 is inactive (EC 50 >100 μM). Otherwise, when tested against L. infantum amastigotes, 1 and 3 exhibited EC 50 values of 10.3 μM (SI=5.0) and 12.7 μM (SI>15.7), respectively, being 2 inactive (EC 50 >100 μM). Comparing the effects of positive controls benznidazol (EC 50 =6.5 μM and SI>30.7) and miltefosine (EC 50 =10.2 μM and SI=15.2), it was observed a selective antiparasitic activity to diastereomers 2 and 3 against T. cruzi and L. infantum. Considering stereochemical aspects, it was suggested that the configuration of the new stereocenter formed after oxidation of 1 played an important role in the bioactivity against amastigotes of both tested parasites.
(© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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