ArticleAntimicrobial agents and chemotherapy2006
In vitro selection and in vivo efficacy of piperazine- and alkanediamide-linked bisbenzamidines against Pneumocystis pneumonia in mice.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- The Effects of Sex and Strain onJournal of fungi (Basel, Switzerland) · 2022Article
- The Antifungal and Anti-Pneumocystis Activities of the Novel Compound A3IS (Mycosinate).Antimicrobial agents and chemotherapy · 2022Article
- The Persistent Challenge of Pneumocystis Growth Outside the Mammalian Lung: Past and Future Approaches.Frontiers in microbiology · 2021Review
- Article
- Chloroquine Analogues as Leads against Pneumocystis Lung Pathogens.Antimicrobial agents and chemotherapy · 2018Article
- A quantitative systems pharmacology (QSP) model for Pneumocystis treatment in mice.BMC systems biology · 2018Article
- Development of highly active anti-MedChemComm · 2017Article
- Alkanediamide-Linked Bisbenzamidines Are Promising Antiparasitic Agents.Pharmaceuticals (Basel, Switzerland) · 2016Article
- Virtual Screening of Phytochemicals to Novel Target (HAT) Rtt109 in Pneumocystis Jirovecii using Bioinformatics Tools.Journal of clinical and diagnostic research : JCDR · 2016Article
- Probing the relationship between anti-Pneumocystis carinii activity and DNA binding of bisamidines by molecular dynamics simulations.Molecules (Basel, Switzerland) · 2015Article
- Structural aspects of intermolecular interactions in the solid state of 1,4-dibenzylpiperazines bearing nitrile or amidine groups.Acta crystallographica Section B, Structural science, crystal engineering and materials · 2014Article
- Pneumocystis jirovecii Rtt109, a novel drug target for Pneumocystis pneumonia in immunosuppressed humans.Antimicrobial agents and chemotherapy · 2014Article
- Design and synthesis of N¹,N⁵-bis[4-(5-alkyl-1,2,4-oxadiazol-3-yl)phenyl]glutaramides as potential antifungal prodrugs.Molecules (Basel, Switzerland) · 2013Article
- Analogs of pentamidine as potential anti-Pneumocystis chemotherapeutics.European journal of medicinal chemistry · 2012Article
- Susceptibility of Pneumocystis to echinocandins in suspension and biofilm cultures.Antimicrobial agents and chemotherapy · 2011Article
- Bisbenzamidines as antifungal agents. are both amidine functions required to observe an anti-Pneumocystis carinii activity?Molecules (Basel, Switzerland) · 2010Article
- Article
- Synthesis and SAR of alkanediamide-linked bisbenzamidines with anti-trypanosomal and anti-pneumocystis activity.Bioorganic & medicinal chemistry letters · 2009Article
- Pneumocystis workshop: 10th anniversary summary.Eukaryotic cell · 2009Article
- Biofilm formation by Pneumocystis spp.Eukaryotic cell · 2009Article
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Authors and funding
8 authors.
Funding
Abstract
Bisbenzamidines, such as pentamidine isethionate, are aromatic dicationic compounds that are active against Pneumocystis and other microbes but are oftentimes toxic to the host. To identify potential anti-Pneumocystis agents, we synthesized bisbenzamidine derivatives in which the parent compound pentamidine was modified by a 1,4-piperazinediyl, alkanediamide, or 1,3-phenylenediamide moiety as the central linker. Several of the compounds were more active against P. carinii and less toxic than pentamidine in cytotoxicity assays. For this study, we evaluated nine bisbenzamidine derivatives representing a range of in vitro activities, from highly active to inactive, for the treatment of pneumocystosis in an immunosuppressed mouse model. Six of these in vitro-active compounds, 01, 02, 04, 06, 100, and 101, exhibited marked efficacies against infection at a dose of 10 mg/kg of body weight, and four compounds, 01, 04, 100, and 101, showed significant increases in survival versus that of untreated infected control mice. Compound 100 was highly efficacious against the infection at 20 mg/kg and 40 mg/kg, with > 1,000-fold reductions in burden, and resulted in improved survival curves versus those for pentamidine-treated mice (at the same doses). All six bisbenzamidine compounds that exhibited high in vitro activity significantly decreased the infection in vivo; two compounds, 12 and 102, with marked to moderate in vitro activities had slight or no activity in vivo, while compound 31 was inactive in vitro and was also inactive in vivo. Thus, the selection of highly active compounds from in vitro cytotoxicity assays was predictive of activity in the mouse model of Pneumocystis pneumonia. We conclude that a number of these bisbenzamidine compounds, especially compound 100, may show promise as new anti-Pneumocystis drugs.
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