The diamidine DB75 targets the nucleus of Plasmodium falciparum
Abstract Background DB289, [2,5-bis(4-amidinophenyl)furan bis-O -methylamidoxime], is a broad spectrum anti-parasitic compound which has been shown to be effective against malaria in recent clinical trials. DB75, [2,5-bis(4-amidinophenyl)furan], is the active metabolite of this drug. The objective o...
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ftdoajarticles:oai:doaj.org/article:d8e76242d7aa4f9d8a70bc56d0285ff9 2023-05-15T15:08:27+02:00 The diamidine DB75 targets the nucleus of Plasmodium falciparum Meshnick Steven R Tidwell Richard R Purfield Anne E 2009-05-01T00:00:00Z https://doi.org/10.1186/1475-2875-8-104 https://doaj.org/article/d8e76242d7aa4f9d8a70bc56d0285ff9 EN eng BMC http://www.malariajournal.com/content/8/1/104 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-104 1475-2875 https://doaj.org/article/d8e76242d7aa4f9d8a70bc56d0285ff9 Malaria Journal, Vol 8, Iss 1, p 104 (2009) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2009 ftdoajarticles https://doi.org/10.1186/1475-2875-8-104 2022-12-31T08:50:35Z Abstract Background DB289, [2,5-bis(4-amidinophenyl)furan bis-O -methylamidoxime], is a broad spectrum anti-parasitic compound which has been shown to be effective against malaria in recent clinical trials. DB75, [2,5-bis(4-amidinophenyl)furan], is the active metabolite of this drug. The objective of this study was to determine the mechanism of action of DB75 in Plasmodium falciparum . Methods Live parasites were observed by confocal microscopy after treatment with organelle specific dyes and DB75, an inherently fluorescent compound. Parasites were exposed to DB75 and assessed for growth and morphological changes over time using blood smears and light microscopy. Also, to determine if DB75 affects gene transcription, real time PCR was used to monitor transcript levels over time for six developmentally expressed genes, including trophozoite antigen R45-like (PFD1175w), lactate dehydrogenase (PF13_0141), DNA primase (PFI0530c), isocitrate dehydrogenase (PF13_0242), merozoite surface protein-1 (PFI1475w), and merozoite surface protein-7 (PF13_0197). Results The results show that DB75 localizes in the parasite nucleus but not in other organelles. Once rings are exposed, parasites mature to the trophozoite stage and stall. No stage-dependent or gene-specific inhibition of transcription was seen. However, DB75 delayed peak transcription of trophozoite-stage genes. Conclusion Taken together, DB75 appears to concentrate in the nucleus and delay parasite maturation. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 8 1 104 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Meshnick Steven R Tidwell Richard R Purfield Anne E The diamidine DB75 targets the nucleus of Plasmodium falciparum |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background DB289, [2,5-bis(4-amidinophenyl)furan bis-O -methylamidoxime], is a broad spectrum anti-parasitic compound which has been shown to be effective against malaria in recent clinical trials. DB75, [2,5-bis(4-amidinophenyl)furan], is the active metabolite of this drug. The objective of this study was to determine the mechanism of action of DB75 in Plasmodium falciparum . Methods Live parasites were observed by confocal microscopy after treatment with organelle specific dyes and DB75, an inherently fluorescent compound. Parasites were exposed to DB75 and assessed for growth and morphological changes over time using blood smears and light microscopy. Also, to determine if DB75 affects gene transcription, real time PCR was used to monitor transcript levels over time for six developmentally expressed genes, including trophozoite antigen R45-like (PFD1175w), lactate dehydrogenase (PF13_0141), DNA primase (PFI0530c), isocitrate dehydrogenase (PF13_0242), merozoite surface protein-1 (PFI1475w), and merozoite surface protein-7 (PF13_0197). Results The results show that DB75 localizes in the parasite nucleus but not in other organelles. Once rings are exposed, parasites mature to the trophozoite stage and stall. No stage-dependent or gene-specific inhibition of transcription was seen. However, DB75 delayed peak transcription of trophozoite-stage genes. Conclusion Taken together, DB75 appears to concentrate in the nucleus and delay parasite maturation. |
format |
Article in Journal/Newspaper |
author |
Meshnick Steven R Tidwell Richard R Purfield Anne E |
author_facet |
Meshnick Steven R Tidwell Richard R Purfield Anne E |
author_sort |
Meshnick Steven R |
title |
The diamidine DB75 targets the nucleus of Plasmodium falciparum |
title_short |
The diamidine DB75 targets the nucleus of Plasmodium falciparum |
title_full |
The diamidine DB75 targets the nucleus of Plasmodium falciparum |
title_fullStr |
The diamidine DB75 targets the nucleus of Plasmodium falciparum |
title_full_unstemmed |
The diamidine DB75 targets the nucleus of Plasmodium falciparum |
title_sort |
diamidine db75 targets the nucleus of plasmodium falciparum |
publisher |
BMC |
publishDate |
2009 |
url |
https://doi.org/10.1186/1475-2875-8-104 https://doaj.org/article/d8e76242d7aa4f9d8a70bc56d0285ff9 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 8, Iss 1, p 104 (2009) |
op_relation |
http://www.malariajournal.com/content/8/1/104 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-104 1475-2875 https://doaj.org/article/d8e76242d7aa4f9d8a70bc56d0285ff9 |
op_doi |
https://doi.org/10.1186/1475-2875-8-104 |
container_title |
Malaria Journal |
container_volume |
8 |
container_issue |
1 |
container_start_page |
104 |
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1766339808646397952 |