New Antimalarial Drugs

Wiesner, Jochen; Ortmann, Regina; Jomaa, Hassan; Schlitzer, Martin

doi:10.1002/chin.200408320

Cited by 52 publications

(89 citation statements)

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“…Some drugs are currently available, alone or in association with other antimalarials (Wiesner et al, 2003;Baird, 2005), but the development of new molecules remains a priority in the absence of an efficient vaccine strategy.…”

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confidence: 99%

IN VITRO METABOLISM OF FERROQUINE (SSR97193) IN ANIMAL AND HUMAN HEPATIC MODELS AND ANTIMALARIAL ACTIVITY OF MAJOR METABOLITES ON PLASMODIUM FALCIPARUM

Daher¹,

Pélinski²,

Klieber³

et al. 2006

Drug Metab Dispos

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ABSTRACT:Ferroquine (SSR97193) has been shown to be a promising antimalarial, both on laboratory clones and on field isolates. So far, no resistance was documented in Plasmodium falciparum. In the present work, the metabolic pathway of ferroquine, based on experiments using animal and human hepatic models, is proposed. Ferroquine is metabolized mainly via an oxidative pathway into the major metabolite mono-N-demethyl ferroquine and then into di-N,N-demethyl ferroquine. Some other minor metabolic pathways were also identified. Cytochrome P450 isoforms 2C9, 2C19, and 3A4 and, possibly in some patients, isoform 2D6, are mainly involved in ferroquine oxidation. The metabolites were synthesized and tested against the 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) P. falciparum strains. According to the results, the activity of the two main metabolites decreased compared with that of ferroquine; however, the activity of the mono-N-demethyl derivative is significantly higher than that of chloroquine on both strains, and the di-N-demethyl derivative remains more active than chloroquine on the chloroquine-resistant strain. These results further support the potential use of ferroquine against human malaria.

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confidence: 99%

IN VITRO METABOLISM OF FERROQUINE (SSR97193) IN ANIMAL AND HUMAN HEPATIC MODELS AND ANTIMALARIAL ACTIVITY OF MAJOR METABOLITES ON PLASMODIUM FALCIPARUM

Daher¹,

Pélinski²,

Klieber³

et al. 2006

Drug Metab Dispos

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“…Approximately 40% of the world population lives at risk of this disease and this constitutes a large burden on the health and economic development of low-incomes countries [1][2][3]. Although the World Malaria Report 2011 showed that there has been significant and durable progress in battling this disease, emergence of parasite resistance to antimalarial medicines remains a threat to this continued stride toward the reduction of malaria cases in the world.…”

Section: Introductionmentioning

confidence: 99%

Development of Plasmodium falciparum Protease Inhibitors in the Past Decade (2002–2012)

Pérez

Teixeira

Gomes³

et al. 2013

CMC

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New drug targets for the development of antimalarial drugs have emerged after the unveiling of the Plasmodium falciparum genome in 2002. Potential antimalarial drug targets can be broadly classified into three categories according to their function in the parasite's life cycle: (i) biosynthesis, (ii) membrane transport and signaling, and (iii) hemoglobin catabolism. The latter plays a key role, as inhibition of hemoglobin degradation impairs maturation of bloodstage malaria parasites, ultimately leading to remission or even cure of the most severe stage of the infection. Intraerythrocytic Plasmodia parasites have limited capacity to biosynthesize amino acids which are vital for their growth. Therefore, the parasites obtain those essential amino acids via degradation of host cell hemoglobin, making this a crucial process for parasite survival. Several plasmodial proteases are involved in hemoglobin catabolism, among which plasmepsins and falcipains are well-known examples. Hence, development of P. falciparum protease inhibitors is a promising approach to antimalarial chemotherapy, as highlighted by the present review which is focused on the Medicinal Chemistry research effort recorded in the past decade in this particular field.

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“…Estimates range from 300 to 500 million clinical cases of malaria each year and approximately 1.5-2.5 million die due to non-availability of a proper therapeutic agent [1][2][3] . During the past four decades, chloroquine (CQ) and other aminoquinolines have been the mainstays of malarial chemotherapy due to their therapeutic efficacy 4 .…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis of 4-aminoquinoline-derived thiazolidines and their antimalarial activity and heme polymerization inhibition studies

Solomon

Haq

Srivastava

et al. 2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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New Antimalarial Drugs

Abstract: For Abstract see ChemInform Abstract in Full Text.

Cited by 52 publications

References 1 publication

IN VITRO METABOLISM OF FERROQUINE (SSR97193) IN ANIMAL AND HUMAN HEPATIC MODELS AND ANTIMALARIAL ACTIVITY OF MAJOR METABOLITES ON PLASMODIUM FALCIPARUM

IN VITRO METABOLISM OF FERROQUINE (SSR97193) IN ANIMAL AND HUMAN HEPATIC MODELS AND ANTIMALARIAL ACTIVITY OF MAJOR METABOLITES ON PLASMODIUM FALCIPARUM

Development of Plasmodium falciparum Protease Inhibitors in the Past Decade (2002–2012)

Design, synthesis of 4-aminoquinoline-derived thiazolidines and their antimalarial activity and heme polymerization inhibition studies

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