Journal of Medicinal Chemistry
Brief Article
*
K.; Weinberg, J. B.; Price, R. N.; Duffull, S. B.; Celermajer, D. S.;
Anstey, N. M. Increased asymmetric dimethylarginine in severe
falciparum malaria: association with impaired nitric oxide bioavail-
ability and fatal outcome. PLoS Pathog. 2010, 6, e1000868.
(10) Cabrales, P.; Zanini, G. M.; Meays, D.; Frangos, J. A.; Carvalho,
L. J. Murine cerebral malaria is associated with a vasospasm-like
microcirculatory dysfunction, and survival upon rescue treatment is
markedly increased by nimodipine. Am. J. Pathol. 2010, 176, 1306−
315.
11) Cabrales, P.; Martins, Y. C.; Ong, P. K.; Zanini, G. M.; Frangos,
J. A.; Carvalho, L. J. M. Cerebral tissue oxygenation impairment during
experimental cerebral malaria. Virulence 2013, 4, 686−697.
12) Ong, P. K.; Melchior, B.; Martins, Y. C.; Hofer, A.; Orjuela-
́
Sanchez, P.; Cabrales, P.; Zanini, G. M.; Frangos, J. A.; Carvalho, L. J.
Nitric oxide synthase dysfunction contributes to impaired cerebroar-
Author Contributions
#
M.B. and P.O.-S. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by National Institutes of Health
NIH) Grant R01-AI82610 to L.J.M.C. and by University of
■
(
1
(
Torino (Ricerca Locale, Grant 2013). L.J.M.C. is recipient of a
Research Productivity Fellowship from CNPq and a CNE grant
from Faperj, Brazil.
(
ABBREVIATIONS USED
teriolar reactivity in experimental cerebral malaria. PLoS Pathog. 2013,
■
9
(
, e1003444.
13) Cabrales, P.; Zanini, G. M.; Meays, D.; Frangos, J. A.; Carvalho,
CM, cerebral malaria; SM, severe malaria; ECM, experimental
cerebral malaria; BBB, blood−brain barrier; eNOS, endothelial
nitric oxide synthase; nNOS, neuronal nitric oxide synthase;
AIBN, azabisisobutyronitrile; NBS, N-bromosuccinimide;
mCPBA, m-chloroperbenzoic acid; DCC, dicyclohexylcarbodii-
mide; DMAP, 4-dimethylaminopyridine; ODQ, 1H-[1,2,4]-
oxadiazole[4,3-a]quinoxalin-1-one; sGC, soluble guanylate
cyclase
L. J. Nitric oxide protection against murine cerebral malaria is
associated with improved cerebral microcirculatory physiology. J.
Infect. Dis. 2011, 203, 1454−1463.
(14) Zanini, G. M.; Cabrales, P.; Barkho, W.; Frangos, J. A.;
Carvalho, L. J. Exogenous nitric oxide decreases brain vascular
inflammation, leakage and venular resistance during Plasmodium
berghei ANKA infection in mice. J. Neuroinflammation 2011, 8, 66.
(15) Zanini, G. M.; Martins, Y. C.; Cabrales, P.; Frangos, J. A.;
Carvalho, L. J. S-nitrosoglutathione prevents experimental cerebral
REFERENCES
■
malaria. J. Neuroimmune Pharmacol. 2012, 7, 477−487.
(
(
1) World Malaria Report 2014; WHO: Geneva, Switzerland, 2014.
2) Dondorp, A. M.; Fanello, C. I.; Hendriksen, I. C.; Gomes, E.;
(16) Orjuela-Sanchez, P.; Ong, P. K.; Melchior, B.; Zanini, G. M.;
Martins, Y. C.; Meays, D.; Frangos, J. A.; Carvalho, L. J. Transdermal
glyceryl trinitrate as an effective adjunctive treatment with artemether
for late stage experimental cerebral malaria. Antimicrob. Agents
Seni, A.; Chhaganlal, K. D.; Bojang, K.; Olaosebikan, R.; Anunobi, N.;
Maitland, K.; Kivaya, E.; Agbenyega, T.; Nguah, S. B.; Evans, J.;
Gesase, S.; Kahabuka, C.; Mtove, G.; Nadjm, B.; Deen, J.; Mwanga-
Amumpaire, J.; Nansumba, M.; Karema, C.; Umulisa, N.; Uwimana,
A.; Mokuolu, O. A.; Adedoyin, O. T.; Johnson, W. B.; Tshefu, A. K.;
Onyamboko, M. A.; Sakulthaew, T.; Ngum, W. P.; Silamut, K.;
Stepniewska, K.; Woodrow, C. J.; Bethell, D.; Wills, B.; Oneko, M.;
Peto, T. E.; von Seidlein, L.; Day, N. P.; White, N. J. AQUAMAT
group. Artesunate versus quinine in the treatment of severe falciparum
malaria in African children (AQUAMAT): an open-label, randomised
trial. Lancet 2010, 376, 1647−1657.
(18) Bertinaria, M.; Guglielmo, S.; Rolando, B.; Giorgis, M.; Aragno,
C.; Fruttero, R.; Gasco, A.; Parapini, S.; Taramelli, D.; Martins, Y. C.;
Carvalho, L. J. Amodiaquine analogues containing NO-donor
substructures: synthesis and their preliminary evaluation as potential
tools in the treatment of cerebral malaria. Eur. J. Med. Chem. 2011, 46,
(
3) Carter, J. A.; Mung’ala-Odera, V.; Neville, B. G.; Murira, G.;
Mturi, N.; Musumba, C.; Newton, C. R. Persistent neurocognitive
impairments associated with severe falciparum malaria in Kenyan
children. J. Neurol., Neurosurg. Psychiatry 2005, 76, 476−481.
1
(
757−1767.
19) Miller, L. H.; Ackerman, H. C.; Su, X.; Wellems, T. E. Malaria
biology and disease pathogenesis: insights for new treatments. Nat.
Med. 2013, 19, 156−167.
(
4) Mishra, S. K.; Newton, C. R. Diagnosis and management of the
neurological complications of falciparum malaria. Nat. Rev. Neurol.
009, 5, 189−198.
5) Gramaglia, I.; Sobolewski, P.; Meays, D.; Contreras, R.; Nolan, J.
(
́
20) Orjuela-Sanchez, P.; Duggan, E.; Nolan, J.; Frangos, J. A.;
2
(
Carvalho, L. J. A lactate dehydrogenase ELISA-based assay for the in
vitro determination of Plasmodium berghei sensitivity to anti-malarial
drugs. Malar. J. 2012, 11, 366.
P.; Frangos, J. A.; Intaglietta, M.; van der Heyde, H. C. Low nitric
oxide bioavailability contributes to the genesis of experimental cerebral
malaria. Nat. Med. 2007, 12, 1417−1422.
(21) Clemmer, L.; Martins, Y. C.; Zanini, G. M.; Frangos, J. A.;
Carvalho, L. J. Artemether and artesunate show the highest efficacies
in rescuing mice with late-stage cerebral malaria and rapidly decrease
leukocyte accumulation in the brain. Antimicrob. Agents Chemother.
(
6) Yeo, T. W.; Lampah, D. A.; Gitawati, R.; Tjitra, E.; Kenangalem,
E.; McNeil, Y. R.; Darcy, C. J.; Granger, D. L.; Weinberg, J. B.;
Lopansri, B.; Price, R. N.; Duffull, S. B.; Celermajer, D. S.; Anstey, N.
M. Impaired nitric oxide bioavailability and L-arginine reversible
endothelial dysfunction in adults with falciparum malaria. J. Exp. Med.
007, 204, 2693−2704.
7) Anstey, N. M.; Weinberg, J. B.; Hassanali, M. Y.; Mwaikambo, E.
2
(
011, 55, 1383−1390.
22) Bohn, H.; Brendel, J.; Martorana, P. A.; Shoenafinger, K.
Cardiovascular Actions of the furoxan CAS 1609, a novel nitric oxide
donor. Br. J. Pharmacol. 1995, 114, 1605−1612.
2
(
D.; Manyenga, D.; Misukonis, M. A.; Arnelle, D. R.; Hollis, D.;
McDonald, M. I.; Granger, D. L. Nitric oxide in Tanzanian children
with malaria: inverse relationship between malaria severity and nitric
oxide production/nitric oxide synthase type 2 expression. J. Exp. Med.
1
(
996, 184, 557−567.
8) Lopansri, B. K.; Anstey, N. M.; Weinberg, J. B.; Stoddard, G. J.;
Hobbs, M. R.; Levesque, M. C.; Mwaikambo, E. D.; Granger, D. L.
Low plasma arginine concentrations in children with cerebral malaria
and decreased nitric oxide production. Lancet 2003, 361, 676−678.
(
9) Yeo, T. W.; Lampah, D. A.; Tjitra, E.; Gitawati, R.; Darcy, C. J.;
Jones, C.; Kenangalem, E.; McNeil, Y. R.; Granger, D. L.; Lopansri, B.
E
J. Med. Chem. XXXX, XXX, XXX−XXX