Molecular epidemiology of malaria in Yaounde, Cameroon V. analysis of the omega repetitive region of the plasmodium falciparum CG2 gene and chloroquine resistance.

Basco, Léonardo K.; Ringwald, Pascal

doi:10.4269/ajtmh.1999.61.807

Cited by 21 publications

(16 citation statements)

References 36 publications

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“…Structurally related tricyclic antihistaminic compounds examined in this study exerted different intrinsic activity but the same chloroquine-potentiating activity. The IC 50 value for chloroquine against W2 parasites was found to decrease by 50% using verapamil at a concentration of 0.8 M and promethazine at 0.5 M. These findings agree with previous published data on W2 parasites. 29 Verapamil, when used at concentrations between 0.5 M and 1 M, was found to reverse the chloroquine resistance between 40% and 85%.…”

Section: Discussionsupporting

confidence: 92%

“…29 Verapamil, when used at concentrations between 0.5 M and 1 M, was found to reverse the chloroquine resistance between 40% and 85%. 9,20,29 Promethazine at a concentration of 1 M has been found to decrease the chloroquine IC 50 value by 90%. 20 Our tricyclic antihistaminic compounds show a 50% decrease in …”

Section: Discussionmentioning

confidence: 97%

“…Data were analyzed after logarithmic transformation and expressed as the geometric mean IC 50 and 95% confidence intervals (CIs) were calculated.…”

Section: Strains Ofmentioning

confidence: 99%

“…The different DEA derivatives fractional IC 50 was calculated by dividing their fixed concentrations by the IC 50 of tested drugs alone and plotted on the horizontal axis. The corresponding chloroquine fractional IC 50 was calculated by dividing the IC 50 of chloroquine combined with fixed concentrations of DEA derivatives and plotted on the vertical axis. Points lying above the straight diagonal line (corresponding to the points where there is no interaction between the drugs) are antagonistic, points below the straight diagonal line are considered to be synergistic.…”

Section: Strains Ofmentioning

confidence: 99%

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In vitro reversal of chloroquine resistance in Plasmodium falciparum with dihydroethanoanthracene derivatives.

Pradines¹,

Alibert²,

Houdoin³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. The effects of combining four dihydroethanoanthracenic (DEA) derivatives and chloroquine were assessed in vitro against Plasmodium falciparum chloroquine resistant parasites W2, Palo Alto, FCR3, and Bres1. Like verapamil or promethazine, the four dihydroethanoanthracenic derivatives tested can be added to the growing list of agents that show capability in enhancing the activity of chloroquine against resistant parasites. The structurally related tricyclic antihistaminic compounds examined in this study exerted different intrinsic antimalarial activity, but the same chloroquine-potentiating activity as verapamil or promethazine. They may act both on the rate of chloroquine accumulation and on its access to ferriprotoporphyrin IX. The reversal mechanism would be assumed to result from competition between DEA derivatives and chloroquine for efflux translocation sites, thus causing an increase in steadystate accumulation of chloroquine and a return to susceptibility. Restoration of therapeutic efficacy of chloroquine against resistant parasites by the administration of an additional drug available at relatively low cost may be a more effective strategy than the introduction of another antimalarial drug at the national level.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 97%

“…Data were analyzed after logarithmic transformation and expressed as the geometric mean IC 50 and 95% confidence intervals (CIs) were calculated.…”

Section: Strains Ofmentioning

confidence: 99%

Section: Strains Ofmentioning

confidence: 99%

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In vitro reversal of chloroquine resistance in Plasmodium falciparum with dihydroethanoanthracene derivatives.

Pradines¹,

Alibert²,

Houdoin³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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“…This Cg2 molecule could therefore be implicated in CQ transport and in the inhibition of ferriprotoporphyrin IX polymerization. Polymorphisms in cg2 were highly associated with CQ resistance (8), but allelic modification experiments have ruled out a role for this gene in CQ resistance (25).…”

mentioning

confidence: 99%

In Vitro Increase in Chloroquine Accumulation Induced by Dihydroethano- and Ethenoanthracene Derivatives in Plasmodium falciparum -Parasitized Erythrocytes

Pradines

Alibert

Houdoin

et al. 2002

Antimicrob Agents Chemother

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The effects of a series of dihydroethano-and ethenoanthracene derivatives on chloroquine (CQ) accumulation in CQ-susceptible strain 3D7 and CQ-resistant clone W2 were assessed. The levels of CQ accumulation increased little or none in CQ-susceptible strain 3D7 and generally increased markedly in CQ-resistant strain W2. At 10 M, 28 compounds yielded cellular accumulation ratios (CARs) greater than that observed with CQ alone in W2. At 10 M, in strain W2, 21 of 31 compounds had CQ CARs two or more times higher than that of CQ alone, 15 of 31 compounds had CQ CARs three or more times higher than that of CQ alone, 13 of 31 compounds had CQ CARs four or more times higher than that of CQ alone, and 9 of 31 compounds had CQ CARs five or more times higher than that of CQ alone. At 1 M, 17 of 31 compounds had CQ CARs two or more times higher than that of CQ alone, 12 of 31 compounds had CQ CARs three or more times higher than that of CQ alone, 6 of 31 compounds had CQ CARs four or more times higher than that of CQ alone, and 3 of 31 compounds had CQ CARs five or more times higher than that of CQ alone. At 1 M, 17 of 31 compounds were more potent inducers of CQ accumulation than verapamil and 12 of 31 compounds were more potent inducers of CQ accumulation than promethazine. The nature of the basic group seems to be associated with increases in the levels of CQ accumulation. At 1 and 10 M, 10 of 14 and 13 of 14 compounds with amino group (amines and diamines), respectively, had CARs >3, while at 1 and 10 M, only 1 of the 13 derivatives with amido groups had CARs >3. Among 12 of the 31 compounds which were more active inducers of CQ accumulation than promethazine at 1 M, 10 had amino groups and 1 had an amido group.

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Antimalarial Agents

Casteel¹

2003

Burger's Medicinal Chemistry and Drug Discovery

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Malaria continues to be a major global health problem and seems to be increasing in some parts of the world. By way of an introduction, relevant aspects of the disease, including incidence and resistance, and of the parasite and its biochemistry and genetics are presented. The chemotherapeutic agents now available to prevent and treat malaria are discussed individually. Some of these drugs have been in use for decades or even centuries, such as quinine, chloroquine, and primaquine. Other agents are of more recent origin including mefloquine, halofantrine, atovaquone, and the artemisinins. Chloroquine had been the drug of first resort for many years. It is inexpensive, well‐tolerated, and extremely effective where parasites remain sensitive. But the development of resistance to chloroquine has emphasized the need for new agents and strategies to treat malaria. New information on the genetic basis of chloroquine resistance and on the overall mechanism of action of chloroquine holds promise for advances in therapy. Another important tactic in dealing with infection by resistant parasites is the use of drug combinations. The combination of pyrimethamine and sulfadoxine has been very successful, but resistance is developing. Newer, highly effective combinations include atovaquone with proguanil, lumefantrine with artemether, and chlorproguanil with dapsone. The artemisinin group of compounds has made a powerful positive impact on malaria chemotherapy although their use in monotherapy is not recommended. Details of the mechanism of action of these drugs are becoming clearer. Knowledge about action should assist in addressing issues of possible toxicity. Great progress has been made in sequencing the genome of Plasmodium falciparum . New molecular targets have been identified as a result and efforts are underway to develop antimalarial agents based on these targets. Researchers around the world are also exploring natural products for yet another lead in antimalarial chemotherapy. “If we take as our standard of importance the greatest harm to the greatest number, then there is no question that malaria is the most important of all infectious diseases 1 .” “Ah, poor heart! he is so shaked of a burning quotidian tertian, that it is most lamentable to behold [2].”

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Molecular epidemiology of malaria in Yaounde, Cameroon V. analysis of the omega repetitive region of the plasmodium falciparum CG2 gene and chloroquine resistance.

Cited by 21 publications

References 36 publications

In vitro reversal of chloroquine resistance in Plasmodium falciparum with dihydroethanoanthracene derivatives.

In vitro reversal of chloroquine resistance in Plasmodium falciparum with dihydroethanoanthracene derivatives.

In Vitro Increase in Chloroquine Accumulation Induced by Dihydroethano- and Ethenoanthracene Derivatives in Plasmodium falciparum -Parasitized Erythrocytes

Antimalarial Agents

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