ArticlePharmaceutical research2002
Enhanced permeability of the antimicrobial agent 2,5-bis(4-amidinophenyl)furan across Caco-2 cell monolayers via its methylamidoidme prodrug.
Article in Pharmaceutical research, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Novel amidines and analogues as promising agents against intracellular parasites: a systematic review.Parasitology · 2013Pooled it
- Development of a Hierarchical Support Vector Regression-Based In Silico Model for Caco-2 Permeability.Pharmaceutics · 2021Article
- New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story.Tropical medicine and infectious disease · 2020Review
- Chemotherapy of second stage human African trypanosomiasis: comparison between the parenteral diamidine DB829 and its oral prodrug DB868 in vervet monkeys.PLoS neglected tropical diseases · 2015Article
- CYP1A1 and CYP1B1-mediated biotransformation of the antitrypanosomal methamidoxime prodrug DB844 forms novel metabolites through intramolecular rearrangement.Journal of pharmaceutical sciences · 2014Article
- Compartmental and enzyme kinetic modeling to elucidate the biotransformation pathway of a centrally acting antitrypanosomal prodrug.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- A semiphysiologically based pharmacokinetic modeling approach to predict the dose-exposure relationship of an antiparasitic prodrug/active metabolite pair.Drug metabolism and disposition: the biological fate of chemicals · 2012Article
- Interactions of DB75, a novel antimalarial agent, with other antimalarial drugs in vitro.Antimicrobial agents and chemotherapy · 2008Article
- The mitochondrion is a site of trypanocidal action of the aromatic diamidine DB75 in bloodstream forms of Trypanosoma brucei.Antimicrobial agents and chemotherapy · 2008Article
- Human enteric microsomal CYP4F enzymes O-demethylate the antiparasitic prodrug pafuramidine.Drug metabolism and disposition: the biological fate of chemicals · 2007Article
- Prodrugs for the treatment of neglected diseases.Molecules (Basel, Switzerland) · 2007Review
- CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O-demethylation of the antiparasitic prodrug DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime].Drug metabolism and disposition: the biological fate of chemicals · 2006Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
purposeDB75 [2.5-bis(4-amidinophenyl)furan] is a promising antimicrobial agent although it has poor oral potency. In contrast, its novel prodrug, 2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime (DB289). has excellent oral potency. The mechanisms of transport of DB289 and DB75 across intestinal epithelium have been investigated in these studies to understand differences in their oral potency.
methodsCaco-2 cell monolayers were used as an in vitro model to examine the mechanisms of transport of DB289 and DB75. Samples collected from the transport studies were quantified using high-performance liquid chromatography with ultraviolet and fluorescence detection.
resultsA low permeability coefficient (3.8 x 10(-7) cm/s for transport in apical [AP] to basolateral [BL] direction) and high sensitivity to extracellular Ca2+ suggest that AP to BL transport of DB75 across Caco-2 cell monolayers occurs predominantly via a paracellular route. DB289 has an 85-fold higher transport rate (322.0 x 10(-7) cm/s for transport in the AP to BL direction) across Caco-2 monolayers than that of DB75. This, with its insensitivity to extracellular Ca2+ indicates that AP to BL transport of DB289 across Caco-2 cell monolayers occurs predominantly via a transcellular route.
conclusionsDB75 is transported across Caco-2 cell monolayers predominantly via paracellular pathways, whereas the prodrug DB289 is transported via transcellular pathways. This could account for the much higher oral activity of DB289 over DB75.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.