ArticleAntimicrobial agents and chemotherapy2004
Highly active anti-Pneumocystis carinii compounds in a library of novel piperazine-linked bisbenzamidines and related compounds.
Article in Antimicrobial agents and chemotherapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Development of highly active anti-MedChemComm · 2017Article
- The Celecoxib Derivative AR-12 Has Broad-Spectrum Antifungal Activity In Vitro and Improves the Activity of Fluconazole in a Murine Model of Cryptococcosis.Antimicrobial agents and chemotherapy · 2016Article
- Pentamidine analogs as inhibitors of [(3)H]MK-801 and [(3)H]ifenprodil binding to rat brain NMDA receptors.Bioorganic & medicinal chemistry · 2015Article
- 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
- Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in Vivo Study.Pharmaceuticals (Basel, Switzerland) · 2013Article
- Analogs of pentamidine as potential anti-Pneumocystis chemotherapeutics.European journal of medicinal chemistry · 2012Article
- Novel piperazine induces apoptosis in U937 cells.International journal of biochemistry and molecular biology · 2011Article
- Bisbenzamidines as antifungal agents. are both amidine functions required to observe an anti-Pneumocystis carinii activity?Molecules (Basel, Switzerland) · 2010Article
- Imidazoquines as antimalarial and antipneumocystis agents.Journal of medicinal chemistry · 2009Article
- Synthesis and SAR of alkanediamide-linked bisbenzamidines with anti-trypanosomal and anti-pneumocystis activity.Bioorganic & medicinal chemistry letters · 2009Article
- Microarray analysis of the in vivo sequence preferences of a minor groove binding drug.BMC genomics · 2008Article
- In vitro selection and in vivo efficacy of piperazine- and alkanediamide-linked bisbenzamidines against Pneumocystis pneumonia in mice.Antimicrobial agents and chemotherapy · 2006Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Trimethoprim-sulfamethoxazole and pentamidine isethionate have been used extensively for the prophylaxis and therapy of pneumonia caused by Pneumocystis jirovecii. Problems associated with toxicity and potential emerging resistance for both therapies necessitate the development of safe and effective analogs or new treatment strategies. In the present study, a library of 36 compounds was synthesized by using the pentamidine molecule as the parent compound modified by a 1,4-piperazinediyl moiety as the central linker to restrict conformation flexibility. The compounds were evaluated for anti-Pneumocystis carinii activity in a bioluminescent ATP-driven assay. Four of the compounds were highly active, with 50% inhibitory concentration (IC(50)) values of <0.01 microg/ml; four had very marked activity (IC(50) < 0.10 microg/ml); ten had marked activity (IC(50) < 1.0 microg/ml); nine had moderate activity (IC(50) < 10 microg/ml); one had slight activity (IC(50) = 34.1 microg/ml); and the remaining eight did not demonstrate activity in this assay system. The high level of activity was specifically associated with an alkyl chain length of five to six carbons attached to one of the nitrogens of the bisamidinium groups. None of the highly active compounds and only one of the very marked compounds exhibited any toxicity when evaluated in three mammalian cell lines. The strategy of substitution of 1,4-piperazine-linked bisbenzamidines produced compounds with the highest level of activity observed in the ATP assay and holds great promise for the development of efficacious anti-P. carinii therapy.
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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.