ArticleAntimicrobial agents and chemotherapy2003
Antimalarial 9-anilinoacridine compounds directed at hematin.
Article in Antimicrobial agents and chemotherapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 54 citations in OpenAlex.
- Efficacy, Structure-Activity Relationship, and Mode of Action Studies of a New Generation of Acridine/Acridone-Based Antimalarials.ACS infectious diseases · 2026Article
- Article
- Pyronaridine: a review of its clinical pharmacology in the treatment of malaria.The Journal of antimicrobial chemotherapy · 2023Review
- Acridine-Based Antimalarials-From the Very First Synthetic Antimalarial to Recent Developments.Molecules (Basel, Switzerland) · 2021Review
- Various Parts ofEvidence-based complementary and alternative medicine : eCAM · 2019Article
- Novel carbazole aminoalcohols as inhibitors of β-hematin formation: Antiplasmodial and antischistosomal activities.International journal for parasitology. Drugs and drug resistance · 2017Article
- Design, Synthesis and Evaluation of Bifunctional Acridinine-Naphthalenediimide Redox-Active Conjugates as Antimalarials.ACS omega · 2016Article
- Evidence for pyronaridine as a highly effective partner drug for treatment of artemisinin-resistant malaria in a rodent model.Antimicrobial agents and chemotherapy · 2014Article
- Review of pyronaridine anti-malarial properties and product characteristics.Malaria journal · 2012Article
- Acridine and acridinones: old and new structures with antimalarial activity.The open medicinal chemistry journal · 2011Article
- Novel antimalarial aminoquinolines: heme binding and effects on normal or Plasmodium falciparum-parasitized human erythrocytes.Antimicrobial agents and chemotherapy · 2009Article
- Bis-acridines as lead antiparasitic agents: structure-activity analysis of a discrete compound library in vitro.Antimicrobial agents and chemotherapy · 2007Article
- Targeting of hematin by the antimalarial pyronaridine.Antimicrobial agents and chemotherapy · 2006Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antimalarial 9-anilinoacridines are potent inhibitors of parasite DNA topoisomerase II both in vitro and in situ. 3,6-diamino substitution on the acridine ring greatly improves parasiticidal activity against Plasmodium falciparum by targeting DNA topoisomerase II. A series of 9-anilinoacridines were investigated for their abilities to inhibit beta-hematin formation, to form drug-hematin complexes, and to enhance hematin-induced lysis of red blood cells. Inhibition of beta-hematin formation was minimal with 3,6-diamino analogs of 9-anilinoacridine and greatest with analogs with a 3,6-diCl substitution together with an electron-donating group in the 1'-anilino position. On the other hand, the presence of a 1'-N(CH3)2 group in the anilino ring produced compounds that strongly inhibited beta-hematin formation but which did not appear to be sensitive to the nature of the substitutions in the acridine nucleus. The derivatives bound hematin, and Job's plots of UV-visible absorbance changes in drug-hematin complexes at various molar ratios indicated a stoichiometric ratio of 1:2. The drugs enhanced hematin-induced red blood cell lysis at low concentrations (<4 microM). These studies open up the novel possibility of development of 9-anilinoacridine antimalarials that target not only DNA topoisomerase II but also beta-hematin formation, which should help delay the rapid onset of resistance to drugs acting at only a single site.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.