manauswilson duarte alecrim maria das graças alecrim malaria research in the amazonas state fmt-am...
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Manaus Wilson Duarte AlecrimMaria das Graças Alecrim
Malaria Research in the Amazonas StateFMT-AM
Cuiabá Cor Jesus Fernandes FontesFrancisco Jose Dutra Souto
Nucleus of Infectious and Tropical Diseases in Mato Grosso –UFMT
Brasília Pedro Luiz TauilJoão Barberino SantosElisabeth Carmen Duarte
Nucleus of Tropical Medicine-UFB
Belo-Horizonte
Antoniona U. Krettli Experimental and Human MalariaFIOCRUZ
Luzia Helena CarvalhoLuciano Andrade Moreira
Malaria Molecular Biology and Immunology – FIOCRUZ
Rio de Janeiro
José Daniel Figueroa-VillarLuzineide Wanderley Tinoco
Synthesis, Spectroscopy, Molecular Modeling and Biological Evaluation of Bioactive Compounds –IME
Claudio T. Daniel RibeiroLeonardo CarvalhoMaria F. Ferreira da Cruz
Centre for Malaria Research and TrainingFIOCRUZ
Mariano Gustavo Zalis Malaria Molecular Biology –UFRJ
Solange WardellIsabela Ribeiro
FIOCRUZ/FarmanguinhosDNDi - WHO
São Paulo Hernando A. del Portillo ObandoMaria Del Carmen F. Becerra
Molecular Biology of Plasmodium-USP
Alejandro Miguel Katzin Malaria Drug Resistance –USP
New Drugs
Synthesis and Natural Products
Antoniana Krettli et al.Antimalarial activity of 4-(5-trifluoromethyl-1H-pyrazol-1-yl)-chloroquine analogues
Traditional medicine in Brazil, antimalarial tests and opportunities for malaria control
Antoniana Ursine KRETTLI & M.Graça Lins BRANDÃO
Ampelozyziphus amazonicus, the “Indian beer”
Bidens pilosa, called “picão”,
Figueroa-Villar et al. Synthesis of Derivatives of the 2,4,6-triaminopirimidinas ()
CHO
NaBH4
DMF
CN
CN(90%)
Terc-ButOHTerc-ButOK / THF
NH
H2N NH2
HCl
CN
CN
PIPERIDINAETANOL
N
N
NH2
H2N NH2
(45%)
CN
CN
(60%)
1e=H1f1g
=NO2=OMe
Introduction of new drug regimens
Solange Wardell and coworkers and Isabela Ribeiro
Development of an artesunate / mefloquine co-formulation
• The results of the 500-patient clinical study comparing AS/MQ with existing separate tablet formulations show a very high cure rate for patients in both groups – 94.1% for AS/MQ and 92.0% for the separate tablet formulation.
Assessment of philosseptin-1, a peptide isolated from the cutaneous secretion of Phyllomedusa
hypochondrialis activity, and its activity on the P. falciparum growth.
Carlos Eduardo Tosta
Cor Jesus Fernandes Fontes
Proguanil plus sulfamethoxazole in the treatment of uncomplicated Plasmodium falciparum malaria
• proguanil 100 mg BID plus sulfamethoxazole 1000 mg BID for 7 days
Drug resistance in P. vivax and P. falciparum
• In vitro drug test methodologies for fresh field isolates.
• Molecular mechanisms of drug resistance
Evaluation of Plasmodium falciparum and P. vivax sensitivity
to antimalarials using the DELI-TESTCarvalho LJM; Chehuan-Mello Y, Ferreira-da-Cruz MF, Druilhe P; Alecrim WD, Brasseur P, Daniel-Ribeiro CT.
IC50 Distribution (P. falciparum )
0,1
1
10
100
1000
0 1 2 3 4
nM
ol/L
CLO QUI MEF ART
IC50 Distribution (P. vivax )
0,1
1
10
100
1000
0 1 2CLO
nM
ol/L
Distribution of IC50 (in nMol/ml) for the different drugs assayed for P. falciparum and P. vivax
• to understand the basis of resistance of P. falciparum to antimalarial drugs (including artemisinin) and explore potentials to improve the potency of existing antimalarial drugs such as CQ, AQ and QN.
Molecular determinants of drug response and resistance in P. falciparum of Africa and South America.
Mariano Zalis
Transporters• PF-A0590w, • PFC0125w, • PF11-0225, • PF13-0271, • PF11-0466, • PF14-0321, • PF13-0019,• PFB0465c, • PFL1125w• PFL0620c
• PFE1185w,
• PF14-0679,
• PF14-0292,
• PFE0775c,
• PF08-0078,
• PF14-0244,
• PF14-0133,
• PFL1410c,
• PfATP6
In vitro sensitivity for Quinineamino acid position
ISOLATE ORIGIN 191
437 657
PVL558 Pt. Velho/BR
MCP120 Macapá/BR
MCP120 Macapá/BR
RBR710 Rondônia/BR
BEL307 Belém/BR
BEL351 Belém/BR
MCP155 Macapá/BR
RBR710 Rondônia/BR
PVL558 Pt. Velho/BR
MCP120 Macapá/BR
MCP151 Macapá/BR
MCP114 Macapá/BR
MCP186 Macapá/BR
MCP189 Macapá/BR
MCP196 Macapá/BR
MCP197 Macapá/BR
MCP138 Macapá/BR
MCP120 Macapá/BR
MCP116 Macapá/BR
MCP177 Macapá/BR
MCP177 Macapá/BR
MCP191 Macapá/BR
SPO23 B.Ventura/CO
SOP42 B.Ventura/CO
SOP38 B.Ventura/CO
SOP19 B.Ventura/CO
Increase IC5
0 values to quin
ineSNPs analysis of the PFA0590w geneand IC50 valuesto quinine inSouth America
mutation
wild type -3D7
Bra
sil
Col
ômb
ia
IC50 range (38 nM – 257 nM)
Brazil: 161-257 nM
Colombia:(38 – 147 nM)
Modulation of chloroquine sensitivity in P. falciparum by over-expression of a P. vivax ortholog of the chloroquine resistance transporter gene, pfcrt
Juliana M Sa, Marcio M Yamamoto, Carmen Fernandez-Becerra , Thomas E Wellems, Hernando A del Portillo