Antileishmanial and anti-Trypanosoma cruzi activities of

Antileishmanial and anti-Trypanosoma cruzi activities of

Brazilian Chemical Society (SBQ). Division of Medicinal Chemistry. 5th Brazilian Symposium on Medicinal Chemistry
Antileishmanial and anti-Trypanosoma cruzi activities of lichexanthone
derivatives
Micheletti, A. C.1*; Honda, N. K.1; Beatriz, A.1; Albuquerque, S.2
*anamicheletti@gmail
1
2
Departamento de Química, CCET-UFMS, CP 549, 79070-900 Campo Grande - MS, Brazil.
Laboratório de Parasitologia, FCFRP – USP, Ribeirão Preto – SP, Brazil.
Keywords: xanthone, structural modification, Leishmania, Trypanosoma cruzi.
(4)
N.a
41.8
13.7
(7)
N.a
N.a
22.9
(9)
N.a
4.5
N.a
(10)
9.5
5.8
N.a
(14)
35.1
21.7
N.a
(15)
N.a
25.9
N.a
(16)
11.5
21.4
N.a
(17)
10.8
3.0
N.a
(18)
9.1
0.1
N.a
(19)
5.4
7.3
4.1
(20)
6.4
8.8
N.a
(21)
22.9
17.6
N.a
(22)
12.6
22.9
30.6
Introduction
More than 3 billion people are affected by protozoan
diseases such as leishmaniasis, and Chagas’
disease. Because of an increasing resistance
against widely used drugs the discovery of novel
classes of active substances is extremely important.
Several natural and synthetic xanthones and their
derivatives were found to be promising compounds
1
to treat parasites . Herein, we present the
antileishmanial and anti-Trypanosoma cruzi activities
of xanthone derivatives prepared from lichexanthone
(1), isolated from the lichen Parmotrema
lichexanthonicum Eliasaro & Adler.
Results and Discussion
Lichexanthone (1) was used as starting material to
synthesize compounds (2) - (22) (figure 1),
according to methods described by Micheletti et al.
2, 3
(2009, 2010) .
CH3
RO
O
CH3
OH
O
OR
R
Lichexanthone (1) R=CH3
O
O
(5) - (22)
n
R
R=Diethylamino, (11) n=3, (12) n=4, (13) n=5
CH3
R=Dipropylamino, (14) n=3, (15) n=4, (16) n=5
H 3C
R=T-butylamino, (17) n=3, (18) n=4, (19) n=5
CH3
O
R=Piperidinyl, (20) n=3, (21) n=4, (22) n=5
Figure 1. Compounds (1) – (22)
All substances were tested for their in vitro activity
against two Leishmania species and T. cruzi. Table 1
shows the best results (IC50 < 50µM for at least 1
organism).
Table 1. Antileishmanial and anti-Trypanosoma
cruzi activities of xanthone derivatives.
IC50 (µM)
Compounds
(3)
N.a= not active
Conclusions
R=Dimethylamino, (8) n=3, (9) n=4, (10) n=5
H 3C
(4) R=
O
OH
R=Br, (5) n=3, (6) n=4, (7) n=5
Norlichexanthone (2) R=H
(3) R=
n
O
L. major
L. braziliensis
T. cruzi
N.a
N.a
11.2
Nitrogenated xanthone derivatives were in general
more active against L. braziliensis, and this kind of
structure was already described as antileishmanial
4, 5
and antimalarial compounds
. However, their
antiprotozoal activities were not extended to T. cruzi,
and the active substances presented different side
chains.
Acknowledgements
FUNDECT/MS, CAPES and UFMS.
____________________
1
Pontius, A; Krick, A; Kehraus, S; Brun, R; Konig, G. M. J. Nat. Prod.
2008, 71, 1579.
Micheletti, A. C.; Beatriz, A.; Lima, D. P.; Honda, N. K.; Pessoa, C.
O.; Moraes, M. O.; Lotufo, L. V.; Magalhães, H. I. F.; Carvalho, N. C.
P. Quim. Nova. 2009, 32, 12.
3
Micheletti, A. C.; Alessio, G. F.; Lima, D. P.; Beatriz, A.; Lima, D. P.;
Honda, N. K. 13th BMOS-Book of abstracts. 2009.
4
Kelly, J. X.; Ignatushchenko, M. V.; Bouwer, H. G.; Peyton D. H.;
Hinrichs, D. J.; Winter, R. W.; Riscoe, M. Mol. Biochem. Parasitol.
2003, 123, 43.
5
Riscoe, M.; Kelly, J. X.; Winter, R. Cur. Med. Chem. 2005, 12, 2539.
2
5th Brazilian Symposium on Medicinal Chemistry – BrazMedChem2008