Reversal of Chloroquine Resistance in Murine Malaria Parasites by Prostaglandin Derivatives

Chandra, Subhash; St, Ohnishi; Bn, Dhawan

doi:10.4269/ajtmh.1993.48.645

Cited by 13 publications

(7 citation statements)

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“…Other Drugs (Table 7) Other compounds, such as natural alkaloids [145,[194][195][196], antibiotics [197,198], antifungal drugs [199], pyrrolidine derivatives [200][201] and hormones or precursors [202,203], are demonstrated to effectively overcome in vitro the P. falciparum CQ resistance or in vivo the P. berghei or P. yoelii CQ resistance [204].…”

Section: Phenothiazines (Antipsychotic Drugs) (Table 4)mentioning

confidence: 99%

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Henry¹,

Alibert²,

Orlandi-Pradines³

et al. 2006

CDT

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The development and spread of resistance to antimalarial drugs poses a severe and increasing public health threat. Failures of prophylaxis or treatment with quinolines, hydroxynaphthoquinones, sesquiterpene lactones, antifolate drugs and sulfamides are involved in a return malaria-related morbidity and mortality. Resistance is associated with a decrease in accumulation of drugs into the vacuole, which results from a reduced uptake of the drug, an increased efflux or a combination of both. A number of candidate genes in P. falciparum have been proposed to be involved in antimalarial resistance, each concerned in membrane transport. Weaker or stronger associations are seen in P. falciparum between the resistance to quinolines or artemisinin derivatives and codon changes in Pfmdr1, a gene which encodes Pgh-1, an ortholog of one of the P-glycoproteins expressed in multi-drug resistant human cancer cells (ABC transporter). Further analysis has revealed a new gene, Pfcrt, encoding a PfCRT protein, which resembles an anion channel. Codon changes found in the Pfcrt sequence in drug resistant isolates could facilitate the drug efflux through a putative channel. It has been proposed that the reversal of quinoline resistance by verapamil is due to hydrophobic binding to the mutated PfCRT protein. Several compounds have demonstrated in the past decade a promising capability to reverse the antimalarial drug resistance in vitro in parasite isolates, in animal models and in human malaria. These drugs belong to different pharmacological classes such as calcium channel blockers, tricyclic antidepressants, antipsychotic calmodulin antagonists, histamine H1-receptor antagonists, analgesic and antipyretic drugs, non-steroidal anti-inflammatory drugs, and to different chemical classes such as synthetic surfactants, alkaloids from plants used in traditional medicine, pyrrolidinoaminoalkanes and anthracenic derivatives. Here we summarize the progress made in biochemical and genetic basis of antimalarial resistance, emphasizing the recent developments on drugs, which interfere with trans membrane proteins involved in drug efflux or uptake.

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Section: Phenothiazines (Antipsychotic Drugs) (Table 4)mentioning

confidence: 99%

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Henry¹,

Alibert²,

Orlandi-Pradines³

et al. 2006

CDT

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“…The mechanism of production of eicosanoids and oxylipin molecules in these organisms is just beginning to be understood (69)(70)(71). However, over the years many studies have described pronounced effects of oxylipins on the growth and development of the protozoan parasites, and while these pieces of evidence have been scattered, they are compelling indicators that long-chain fatty acids and oxylipins are of critical importance to these organisms (12,21,30,36,52,68,69,70,81,98). Some of the more striking results of these studies include inhibition of growth of Plasmodium falciparum in culture and Plasmodium vinckei petteri and Plasmodium yoelii nigeriensis in vivo by C 18 fatty acids (68), reversal of chloroquine resistance in a resistant strain of Plasmodium berghei when infected mice are treated with prostaglandin analogs, and even direct cytotoxicity towards Toxoplasma gondii by platelet-derived chromboxane A 2 and 13-hydroxyoctadecanoic acid (52,142).…”

Section: Vol 16 2003 Eukaryotic Microbial Eicosanoids and Oxylipinsmentioning

confidence: 99%

Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes

2003

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Oxylipins are oxygenated metabolites of fatty acids. Eicosanoids are a subset of oxylipins and include the prostaglandins and leukotrienes, which are potent regulators of host immune responses. Host cells are one source of eicosanoids and oxylipins during infection; however, another potential source of eicosanoids is the pathogen itself. A broad range of pathogenic fungi, protozoa, and helminths produce eicosanoids and other oxylipins by novel synthesis pathways. Why do these organisms produce oxylipins? Accumulating data suggest that phase change and differentiation in these organisms are controlled by oxylipins, including prostaglandins and lipoxygenase products. The precise role of pathogen-derived eicosanoids in pathogenesis remains to be determined, but the potential link between pathogen eicosanoids and the development of TH2 responses in the host is intriguing. Mammalian prostaglandins and leukotrienes have been studied extensively, and these molecules can modulate Th1 versus Th2 immune responses, chemokine production, phagocytosis, lymphocyte proliferation, and leukocyte chemotaxis. Thus, eicosanoids and oxylipins (host or microbe) may be mediators of a direct host-pathogen “cross-talk” that promotes chronic infection and hypersensitivity disease, common features of infection by eukaryotic pathogens

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“…Other compounds, such as natural alkaloids [262,[308][309][310], antibiotics [311,312], antifungal drugs [313], pyrrolidine derivatives [263,[314][315] and hormones or precursors [316,317], are demonstrated to effectively overcome in vitro the P. falciparum CQ resistance or in vivo the P. berghei or P. yoelii CQ resistance.…”

Section: -Transporter Inhibitors and Modulators Of The Multidrug Resimentioning

confidence: 99%

Chemosensitizers in Drug Transport Mechanisms Involved in Protozoan Resistance

Pradines

Pages²,

Barbe³

2005

CDTID

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The emergence and spread of antiparasitic drug resistance pose a severe and increasing public health threat. Failures in prophylaxis or those in treatment with quinolines, hydroxynaphtoquinones, sesquiterpenic lactones, antifolate drugs, arsenic and antimony containing drugs sulfamides induce reemergence of parasitic-related morbidity and mortality. Resistance is often associated with alteration of drug accumulation into parasites, which results from a reduced uptake of the drug, an increased efflux or, a combination of the two processes. Resistance to quinolines, artemisinin derivatives and arsenicals and expression of an active efflux mechanism are more or less correlated in protozoa like Plasmodium spp., Leishmania spp., and Trypanosoma spp. Various parasite candidate genes have been proposed to be involved in drug resistance, each concerned in membrane transport. Genes encoding membrane glycoproteins, orthologue to the P-glycoproteins identified in MDR human cancer cells, have been described in these resistant pathogens in addition to various membrane proteins involved in drug transport. Several compounds have demonstrated, in the past decade, promising capability to reverse the drug resistance in parasite isolates in vitro, in animal models and for human malaria. These drugs belong to different pharmacological classes such as calcium channel blockers, tricyclic antidepressants, antipsychotic calmodulin antagonists, histamine H1-receptor antagonists, analgesic antipyretic drugs, non-steroidal anti-inflammatory drugs, and to different chemical classes such as synthetic surfactants, alkaloids from plants used in traditional medicine, pyrrolidinoaminoalkanes and derivatives, and anthracene derivatives. Here, are summarized the molecular bases of antiparasitic resistance emphasizing recent developments with compounds acting on trans-membrane proteins involved in drug efflux or uptake.

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Reversal of Chloroquine Resistance in Murine Malaria Parasites by Prostaglandin Derivatives

Cited by 13 publications

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Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Chloroquine Resistance Reversal Agents as Promising Antimalarial Drugs

Production of Eicosanoids and Other Oxylipins by Pathogenic Eukaryotic Microbes

Chemosensitizers in Drug Transport Mechanisms Involved in Protozoan Resistance

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