ArticleJournal of medicinal chemistry2011
A chemotype that inhibits three unrelated pathogenic targets: the botulinum neurotoxin serotype A light chain, P. falciparum malaria, and the Ebola filovirus.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- The Fellowship of Privileged Scaffolds-One Structure to Inhibit Them All.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Repurposing the antimalarial pyronaridine tetraphosphate to protect against Ebola virus infection.PLoS neglected tropical diseases · 2019Article
- Antiviral Agents Against Ebola Virus Infection: Repositioning Old Drugs and Finding Novel Small Molecules.Annual reports in medicinal chemistry · 2018Article
- Antimalarials with Benzothiophene Moieties as Aminoquinoline Partners.Molecules (Basel, Switzerland) · 2017Article
- Development of Small-Molecule Antivirals for Ebola.Medicinal research reviews · 2015Review
- Small molecules with antiviral activity against the Ebola virus.F1000Research · 2015Review
- Machine learning models identify molecules active against the Ebola virusF1000Research · 2015Article
- A high content imaging assay for identification of Botulinum neurotoxin inhibitors.Journal of visualized experiments : JoVE · 2014Article
- Second generation steroidal 4-aminoquinolines are potent, dual-target inhibitors of the botulinum neurotoxin serotype A metalloprotease and P. falciparum malaria.Journal of medicinal chemistry · 2014Article
- 4-Amino-7-chloroquinolines: probing ligand efficiency provides botulinum neurotoxin serotype A light chain inhibitors with significant antiprotozoal activity.Journal of medicinal chemistry · 2013Article
- Recent advances in malaria drug discovery.Bioorganic & medicinal chemistry letters · 2013Review
- High content image based analysis identifies cell cycle inhibitors as regulators of Ebola virus infection.Viruses · 2012Article
- Review
- A limited structural modification results in a significantly more efficacious diazachrysene-based filovirus inhibitor.Viruses · 2012Article
- The synthesis of 2,5-bis(4-amidinophenyl)thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease.European journal of medicinal chemistry · 2012Article
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15 authors.
Funding
Abstract
A 1,7-bis(alkylamino)diazachrysene-based small molecule was previously identified as an inhibitor of the botulinum neurotoxin serotype A light chain metalloprotease. Subsequently, a variety of derivatives of this chemotype were synthesized to develop structure-activity relationships, and all are inhibitors of the BoNT/A LC. Three-dimensional analyses indicated that half of the originally discovered 1,7-DAAC structure superimposed well with 4-amino-7-chloroquinoline-based antimalarial agents. This observation led to the discovery that several of the 1,7-DAAC derivatives are potent in vitro inhibitors of Plasmodium falciparum and, in general, are more efficacious against CQ-resistant strains than against CQ-susceptible strains. In addition, by inhibiting β-hematin formation, the most efficacious 1,7-DAAC-based antimalarials employ a mechanism of action analogous to that of 4,7-ACQ-based antimalarials and are well tolerated by normal cells. One candidate was also effective when administered orally in a rodent-based malaria model. Finally, the 1,7-DAAC-based derivatives were examined for Ebola filovirus inhibition in an assay employing Vero76 cells, and three provided promising antiviral activities and acceptably low toxicities.
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