Synthesis and antimalarial activity of novel bicyclic and tricyclic aza-peroxidesElectronic supplementary information (ESI) available. See DOI: 10.1039/c5ra16781g
For the first time, novel bicyclic 5a-h as well as tricyclic 9a-h aza-peroxides were synthesized using a 1 O 2 -mediated photo-oxygenation methodology as a key step in 52-71% yields in which one of the oxygen atoms of the 1,2,4-trioxane ring has been replaced by a nitrogen atom. The methodology is s...
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Main Authors | , , , , , , , |
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Format | Journal Article |
Published |
01.03.2016
|
Online Access | Get full text |
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Summary: | For the first time, novel bicyclic
5a-h
as well as tricyclic
9a-h
aza-peroxides were synthesized using a
1
O
2
-mediated photo-oxygenation methodology as a key step in 52-71% yields in which one of the oxygen atoms of the 1,2,4-trioxane ring has been replaced by a nitrogen atom. The methodology is simple and is an efficient way to access 1,2-dioxa-4-aza six membered ring compounds. All these compounds were assessed for their
in vitro
antimalarial activity against
Plasmodium falciparum
. Compound
9a
,
9c
and
9f
, the most active compound of the series, showed IC
50
values of 9.43, 8.83 and 5.63 ng mL
−1
, respectively which were found to be comparable to that of the antimalarial drug chloroquine (IC
50
value 5.2 ng mL
−1
). Compound
9f
, the most active compound found in
in vitro
studies, provided 40% protection to infected mice at the dose of 96 mg kg
−1
× 4 days when screened for its antimalarial activity
in vivo
against multidrug-resistant
Plasmodium yoelii nigeriensis
in Swiss mice by the oral route. In this assay, β-arteether and chloroquine, showed 100% suppression of parasitaemia on day 4 and provided 100% and 80% protection, respectively, to the infected mice.
Bicyclic and tricyclic aza-peroxides were synthesized and assessed for their
in vitro
and
in vivo
antimalarial activities against
Plasmodium falciparum
(3D7 strain) and
Plasmodium yoelii nigeriensis
in Swiss mice by an oral route, respectively. |
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Bibliography: | 10.1039/c5ra16781g Electronic supplementary information (ESI) available. See DOI |
ISSN: | 2046-2069 |
DOI: | 10.1039/c5ra16781g |