Antimalarial action of nitrobenzylthioinosine in combination with purine nucleoside antimetabolites.

Abstract:

:The infection of human erythrocytes by two strains of the human malarial parasite, Plasmodium falciparum (FCQ-27 or the multi-drug-resistant strain K-1), markedly changed the transport characteristics of the nucleosides, adenosine and tubercidin, compared to uninfected erythrocytes. A component of the transport of these nucleosides was insensitive to the classical mammalian nucleoside transport inhibitor nitrobenzylthioinosine (NBMPR). In vitro studies with tubercidin demonstrated ID50 values of 0.43 and 0.51 microM for FCQ-27 and K-1, respectively. In addition, the nucleoside transport inhibitors NBMPR, nitrobenzylthioguanosine (NBTGR), dilazep and dipyridamole also independently exhibited antimalarial activity in vitro. The combination of tubercidin and NBMPR or NBTGR in vitro demonstrated synergistic activity, whilst tubercidin together with dilazep or dipyridamole showed subadditive activity. Analysis by HPLC indicated that NBMPR could permeate the infected cell membrane and provided evidence for the catabolism of NBMPR in vitro, with subsequent alteration of the purine pool in the infected erythrocyte. These observations further indicated the possibility of the utilization of cytotoxic nucleosides against P. falciparum infection in conjunction with a nucleoside transport inhibitor to protect the host tissue.

journal_name

Mol Biochem Parasitol

authors

Gero AM,Scott HV,O'Sullivan WJ,Christopherson RI

doi

10.1016/0166-6851(89)90023-6

subject

Has Abstract

pub_date

1989-04-01 00:00:00

pages

87-97

issue

1

eissn

0166-6851

issn

1872-9428

pii

0166-6851(89)90023-6

journal_volume

34

pub_type

杂志文章
  • The fate of ferriprotorphyrin IX in malaria infected erythrocytes in conjunction with the mode of action of antimalarial drugs.

    abstract::The intraerythrocytic malaria parasite digests considerable amounts of its host cell cytosol, which consists mostly of hemoglobin. In order to avert the toxicity of ferriprotorphyrin IX (FP) thus produced, it is generally accepted that FP is polymerized to the non-toxic hemozoin. Investigating the fate of FP in cultur...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(99)00008-0

    authors: Zhang J,Krugliak M,Ginsburg H

    更新日期:1999-03-15 00:00:00

  • Immunological identification of Schistosoma mansoni peptidases.

    abstract::Precipitin arcs formed after immunoelectrophoresis of Schistosoma mansoni egg, worm and cercarial antigens with polyspecific rabbit antisera have been 'stained' at neutral pH with chromogenic enzyme substrates specific for proteases and peptidases. A total of 7 antigenically distinct enzymes with peptidolytic properti...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(88)90153-3

    authors: Doenhoff MJ,Modha J,Curtis RH,Adeoye GO

    更新日期:1988-12-01 00:00:00

  • Identification of peripheral membrane proteins associated with the tubo-vesicular network of Plasmodium falciparum infected erythrocytes.

    abstract::During intracellular development of the malarial parasite numerous membranous vesicles appear in the infected erythrocyte cytoplasm between the parasitophorous vacuolar membrane (PVM) and the erythrocyte plasma membrane. In this study we describe the characterization of a monoclonal antibody which recognizes two major...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(97)00206-5

    authors: Martinez SL,Clavijo CA,Winograd E

    更新日期:1998-03-15 00:00:00

  • Characterization of acyl carrier protein and LytB in Babesia bovis apicoplast.

    abstract::The apicoplast is a highly specialized organelle that mediates required functions in the growth and replication of apicomplexan parasites. Despite structural conservation of the apicoplast among different parasite genera and species, there are also critical differences in the metabolic requirements of different parasi...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2011.10.009

    authors: Caballero MC,Pedroni MJ,Palmer GH,Suarez CE,Davitt C,Lau AO

    更新日期:2012-02-01 00:00:00

  • Expression and substrate specificity of a recombinant cysteine proteinase B of Leishmania braziliensis.

    abstract::The cysteine proteinase B of Leishmania parasites is an important virulence factor. In this study we have expressed, isolated and characterized for the first time a recombinant CPB from Leishmania braziliensis, the causative agent of mucocutaneous leishmaniosis. The mature region of the recombinant CPB shares a high p...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2008.06.005

    authors: Lanfranco MF,Loayza-Muro R,Clark D,Núñez R,Zavaleta AI,Jimenez M,Meldal M,Coombs GH,Mottram JC,Izidoro M,Juliano MA,Juliano L,Arévalo J

    更新日期:2008-10-01 00:00:00

  • The interaction of artemisinin with malarial hemozoin.

    abstract::[14C]Artemisinin was taken up by Plasmodium falciparum in culture and concentrated in hemozoin. In vitro, hemin and artemisinin were found to undergo a chemical reaction forming two major products which were isolated by high-performance liquid chromatography (HPLC). The m/z values of the two products were 856 and 871....

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)90014-0

    authors: Hong YL,Yang YZ,Meshnick SR

    更新日期:1994-01-01 00:00:00

  • Duplication, gene conversion, and genetic diversity in the species-specific acyl-CoA synthetase gene family of Plasmodium falciparum.

    abstract::While genes encoding antigens and other highly polymorphic proteins are commonly found in subtelomeres, it is unusual to find a small family of housekeeping genes in these regions. We found that in the species Plasmodium falciparum only, a non-subtelomeric acyl-CoA synthetase (ACS) gene has expanded into a family of d...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2006.06.004

    authors: Bethke LL,Zilversmit M,Nielsen K,Daily J,Volkman SK,Ndiaye D,Lozovsky ER,Hartl DL,Wirth DF

    更新日期:2006-11-01 00:00:00

  • Mimicry of elastin repetitive motifs by Theileria annulata sporozoite surface antigen.

    abstract::Theileria annulata is an important pathogen of cattle in the tropics. The gene sequence of a sporozoite surface antigen (SPAG-1) is reported. Data is also presented demonstrating that SPAG-1 is synthesised as a large precursor. This antigen, which is a candidate for inclusion in a subunit vaccine, shows a remarkable d...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(92)90012-9

    authors: Hall R,Hunt PD,Carrington M,Simmons D,Williamson S,Mecham RP,Tait A

    更新日期:1992-07-01 00:00:00

  • The complete sequence of a Plasmodium malariae SSUrRNA gene and its comparison to other plasmodial SSUrRNA genes.

    abstract::A gene encoding the small subunit rRNA (SSUrRNA) has been isolated from the human parasite, Plasmodium malariae. The gene has been sequenced. It contains conserved and variable regions which conform to patterns established for other eukaryotic SSUrRNA genes. Comparisons with other SSUrRNA genes from Plasmodium species...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(91)90096-o

    authors: Goman M,Mons B,Scaife J

    更新日期:1991-04-01 00:00:00

  • Identification by extrachromosomal amplification and overexpression of a zeta-crystallin/NADPH-oxidoreductase homologue constitutively expressed in Leishmania spp.

    abstract::A gene which overexpresses a 36-kDa protein (p36) in tunicamycin-resistant Leishmania was mapped by transfection and overexpression to the upstream region of the drug maker in the extrachromosomal amplicon. Complete sequencing of this region revealed a single open reading frame of about 1 kb. Authenticity of the clone...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)90147-3

    authors: Liu X,Chang KP

    更新日期:1994-08-01 00:00:00

  • Gender biased differential alternative splicing patterns of the transcriptional cofactor CA150 gene in Schistosoma mansoni.

    abstract::The complex molecular systems involved in the process of sex-differentiation and fertility in Schistosoma mansoni have not yet been completely described. Using a 4608-element cDNA microarray, we have now determined 90 and 139 genes with significantly (q-value

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2006.07.002

    authors: DeMarco R,Oliveira KC,Venancio TM,Verjovski-Almeida S

    更新日期:2006-12-01 00:00:00

  • Whole-genome comparative RNA expression profiling of axenic and intracellular amastigote forms of Leishmania infantum.

    abstract::Leishmania parasites cycle between the alimentary tract of a sandfly vector as free-living promastigotes and the acidified phagolysosomes of the vertebrate host macrophage as aflagellated amastigotes. The differentiation process can be mimicked in host-free culture by switching promastigotes (e.g. 25 degrees C, neutra...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2008.12.012

    authors: Rochette A,Raymond F,Corbeil J,Ouellette M,Papadopoulou B

    更新日期:2009-05-01 00:00:00

  • Molecular cloning and partial characterization of ribosomal RNA genes from Trypanosoma cruzi.

    abstract::To further analyze the organization of the nuclear rDNA locus in Trypanosoma cruzi, genomic recombinant plasmid clones were constructed and isolated after hybridization with rRNA molecules as hybridization probes. Approximately 11 kilobase pairs from the cistron were cloned in three recombinant plasmids carrying adjac...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(88)90047-3

    authors: Hernández R,Díaz-de Léon F,Castañeda M

    更新日期:1988-01-15 00:00:00

  • The genomic organization of guide RNA genes in kinetoplastid protozoa: several conundrums and their solutions.

    abstract::The guide RNA (gRNA) paradigm states that the uridine (U) insertion/deletion type of RNA editing is mediated by short 3' uridylylated gRNAs that are complementary to specific blocks of mature edited sequence. These gRNAs contain the edited sequence information in the form of guiding purine residues that can base pair ...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章,评审

    doi:10.1016/s0166-6851(97)00037-6

    authors: Simpson L

    更新日期:1997-06-01 00:00:00

  • RNA interference of Schistosoma mansoni cathepsin D, the apical enzyme of the hemoglobin proteolysis cascade.

    abstract::The aspartic protease cathepsin D (Clan AA, Family A1) is expressed in the schistosome gut where it plays an apical role in the digestion of hemoglobin released from ingested erythrocytes. In this report, RNA interference approaches were employed to investigate the effects of knockdown of schistosome cathepsin D. Cult...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2007.10.009

    authors: Morales ME,Rinaldi G,Gobert GN,Kines KJ,Tort JF,Brindley PJ

    更新日期:2008-02-01 00:00:00

  • Sequencing and characterization of an Echinococcus multilocularis DNA probe and its use in the polymerase chain reaction.

    abstract::The nucleotide sequence of the cloned Echinococcus multilocularis DNA probe pAL1 was determined in order to simplify and improve the sensitivity of a diagnostic assay through the application of the polymerase chain reaction (PCR). The insert-specific oligonucleotides BG1 and BG2 define a 2.6-kb fragment in the genomic...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(91)90004-p

    authors: Gottstein B,Mowatt MR

    更新日期:1991-02-01 00:00:00

  • Surface-associated antigens of Brugia malayi L2 and L3 parasites during vector-stage development.

    abstract::Surface and metabolic labeling procedures were used to characterize the composition and the time of expression of Brugia malayi L2 and L3 surface-associated molecules as the larvae develop within the mosquito vector. Larvae were harvested from mosquito tissues at 5 (early L2), 8 (late L2) and 11 (L3) days post-infecti...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(92)90039-m

    authors: Ibrahim MS,Richie TL,Scott AL

    更新日期:1992-05-01 00:00:00

  • RNA interference targeting leucine aminopeptidase blocks hatching of Schistosoma mansoni eggs.

    abstract::Schistosoma mansoni leucine aminopeptidase (LAP) is thought to play a central role in hatching of the miracidium from the schistosome egg. We identified two discrete LAPs genes in the S. mansoni genome, and their orthologs in S. japonicum. The similarities in sequence and exon/intron structure of the two genes, LAP1 a...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2009.05.002

    authors: Rinaldi G,Morales ME,Alrefaei YN,Cancela M,Castillo E,Dalton JP,Tort JF,Brindley PJ

    更新日期:2009-10-01 00:00:00

  • Functional role of lysine 12 in Leishmania major AQP1.

    abstract::Leishmania major aquaglyceroporin (AQP1) is an adventitious metalloid channel that allows the bidirectional movement of arsenite and antimonite. Here we demonstrate that AQP1 is subjected to proteasome-dependent degradation. Treatment of Leishmania promastigotes with the proteasome inhibitor MG132 resulted in increase...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2015.07.005

    authors: Sharma M,Mandal G,Mandal S,Bhattacharjee H,Mukhopadhyay R

    更新日期:2015-06-01 00:00:00

  • Molecular characterization of bifunctional hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase from Plasmodium falciparum.

    abstract::A 2118-base pair gene encoding the bifunctional hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate syntheses of Plasmodium falciparum (pfPPPK-DHPS) was expressed under the control of the T5 promoter in a DHPS-deficient Escherichia coli strain. The enzyme was purified to near homogeneity using nickel affinity...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2004.04.012

    authors: Kasekarn W,Sirawaraporn R,Chahomchuen T,Cowman AF,Sirawaraporn W

    更新日期:2004-09-01 00:00:00

  • Amplification and sequencing of genomic DNA fragments encoding cysteine proteases from protozoan parasites.

    abstract::Cysteine protease gene fragments from three protozoan parasites Trypanosoma cruzi, Trypanosoma brucei, and Entamoeba histolytica were amplified by the polymerase chain reaction (PCR) from genomic DNA using degenerate oligonucleotide primers. The primers used for the amplification were designed based upon amino acid se...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(90)90002-4

    authors: Eakin AE,Bouvier J,Sakanari JA,Craik CS,McKerrow JH

    更新日期:1990-02-01 00:00:00

  • Cathepsin B-like cysteine proteases of Leishmania mexicana.

    abstract::A group of Leishmania mexicana cysteine proteases that differ from those previously found in this protozoon are described. The enzymes characteristically have a preference for peptidyl substrates with a phenylalanyl-valyl-arginyl moiety, do not hydrolyse gelatin in substrate-sodium dodecyl sulphate polyacrylamide gels...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(93)90116-f

    authors: Robertson CD,Coombs GH

    更新日期:1993-12-01 00:00:00

  • Characterization of the Trypanosoma brucei homologue of a Trypanosoma cruzi flagellum-adhesion glycoprotein.

    abstract::An immunodominant 72-kDa surface glycoprotein (Gp72) of Trypanosoma cruzi is involved in adhesion of the flagellum to the cell body (Cooper, R, Ribeiro de Jesus, A and Cross, G.A.M (1993) J. Cell Biol. 122, 149-156). We have characterized a gene, flagellum-adhesion glycoprotein genel (fla1), from Trypanosoma brucei th...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(96)02741-7

    authors: Nozaki T,Haynes PA,Cross GA

    更新日期:1996-11-25 00:00:00

  • A short interspersed repetitive element provides a new 3' acceptor site for trans-splicing in certain ribosomal P2 beta protein genes of Trypanosoma cruzi.

    abstract::Four Trypanosoma cruzi genomic DNA fragments carrying different TcP2 beta genes have been isolated and sequenced. Three of them had a single TcP2 beta gene, while the 3.8-kb-long DNA segment encoding the TcP2 beta-H1.8 locus showed two TcP2 beta genes arranged in tandem. These genes were physically connected by a 428-...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(94)00026-3

    authors: Vazquez MP,Schijman AG,Levin MJ

    更新日期:1994-04-01 00:00:00

  • The Haemonchus contortus UNC-49B subunit possesses the residues required for GABA sensitivity in homomeric and heteromeric channels.

    abstract::Hco-UNC-49 is a GABA receptor from the parasitic nematode Haemonchus contortus that has a relatively low overall sequence similarity to vertebrate GABA receptors but is very similar to the UNC-49 receptor found in the free living nematode Caenorhabditis elegans. While the nematode receptors do share >80% sequence simi...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2011.04.002

    authors: Accardi MV,Forrester SG

    更新日期:2011-07-01 00:00:00

  • Cloning and sequence analysis of the Schistosoma mansoni membrane glycoprotein antigen gene GP22.

    abstract::A family of Schistosoma mansoni proteins (18-22 kDa, pI 5.3-5.8) are biosynthesized in juvenile worms and immunoprecipitated by antibodies uniquely present in protective Fischer rat antiserum. A cDNA clone, lambda gt11-40, expressing epitopes common to this protein family was used to obtain a genomic DNA clone, by hyb...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/0166-6851(91)90132-p

    authors: el-Sherbeini M,Ramadan N,Bostian KA,Knopf PM

    更新日期:1991-11-01 00:00:00

  • Mutagenesis study of the glycosylphosphatidylinositol phospholipase C of Trypanosoma brucei.

    abstract::The glycosylphosphatidylinositol phospholipase C (GPI-PLC) from Trypanosoma brucei is particularly effective in hydrolysing the GPI-anchors of some proteins. The enzyme is inhibited by Zn2+ and p-chloromercurylphenylsulphonic acid, both of which can act as sulphydryl reagents, suggesting that a cysteine residue may be...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(97)00177-1

    authors: Carnall N,Webb H,Carrington M

    更新日期:1997-12-15 00:00:00

  • The varieties of gene amplification, diversification and hypervariability in the human malaria parasite, Plasmodium falciparum.

    abstract::The human malaria parasite, Plasmodium falciparum, is able to evade host cell-mediated and humoral immunity to maintain both persistent and repeated infections. Immune evasion is in part due to a robust repertoire of proteins which participate in host-parasite interactions but also exhibit profound antigenic diversity...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章,评审

    doi:10.1016/j.molbiopara.2009.04.003

    authors: Templeton TJ

    更新日期:2009-08-01 00:00:00

  • Profiling the malaria genome: a gene survey of three species of malaria parasite with comparison to other apicomplexan species.

    abstract::We have undertaken the first comparative pilot gene discovery analysis of approximately 25,000 random genomic and expressed sequence tags (ESTs) from three species of Plasmodium, the infectious agent that causes malaria. A total of 5482 genome survey sequences (GSSs) and 5582 ESTs were generated from mung bean nucleas...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/s0166-6851(01)00371-1

    authors: Carlton JM,Muller R,Yowell CA,Fluegge MR,Sturrock KA,Pritt JR,Vargas-Serrato E,Galinski MR,Barnwell JW,Mulder N,Kanapin A,Cawley SE,Hide WA,Dame JB

    更新日期:2001-12-01 00:00:00

  • Transcriptomic analysis of reduced sensitivity to praziquantel in Schistosoma mansoni.

    abstract::Schistosomiasis is an intravascular parasitic infection estimated to affect over 206 million people, the majority of whom live in Africa where the trematode worms Schistosoma mansoni and Schistosoma haematobium are the major causative agents. While a number of drugs have been used to treat schistosomiasis, praziquante...

    journal_title:Molecular and biochemical parasitology

    pub_type: 杂志文章

    doi:10.1016/j.molbiopara.2018.12.005

    authors: Sanchez MC,Cupit PM,Bu L,Cunningham C

    更新日期:2019-03-01 00:00:00