manauswilson duarte alecrim maria das graças alecrim malaria research in the amazonas state fmt-am...

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