ArticleJournal of medicinal chemistry2012
Design, synthesis, calorimetry, and crystallographic analysis of 2-alkylaminoethyl-1,1-bisphosphonates as inhibitors of Trypanosoma cruzi farnesyl diphosphate synthase.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
- Emergence of terpene chemical communication in insects: Evolutionary recruitment of isoprenoid metabolism.Protein science : a publication of the Protein Society · 2023Article
- An Overview on the Therapeutics of Neglected Infectious Diseases-Leishmaniasis and Chagas Diseases.Frontiers in chemistry · 2021Review
- Identifying Structural Determinants of Product Specificity inBiochemistry · 2020Article
- Bisphosphonate-Based Molecules as Potential New Antiparasitic Drugs.Molecules (Basel, Switzerland) · 2020Review
- Phosphonate and Bisphosphonate Inhibitors of Farnesyl Pyrophosphate Synthases: A Structure-Guided Perspective.Frontiers in chemistry · 2020Review
- Advances in preclinical approaches to Chagas disease drug discovery.Expert opinion on drug discovery · 2019Review
- Synthesis and biological evaluation of 1-alkylaminomethyl-1,1-bisphosphonic acids against Trypanosoma cruzi and Toxoplasma gondii.Bioorganic & medicinal chemistry · 2019Article
- In Vitro and In Vivo Activities of Sulfur-Containing Linear Bisphosphonates against Apicomplexan Parasites.Antimicrobial agents and chemotherapy · 2017Article
- Antiparasitic Activity of Sulfur- and Fluorine-Containing Bisphosphonates against Trypanosomatids and Apicomplexan Parasites.Molecules (Basel, Switzerland) · 2017Article
- The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.Molecules (Basel, Switzerland) · 2016Review
- Structure of human farnesyl pyrophosphate synthase in complex with an aminopyridine bisphosphonate and two molecules of inorganic phosphate.Acta crystallographica. Section F, Structural biology communications · 2014Article
- New insights into molecular recognition of 1,1-bisphosphonic acids by farnesyl diphosphate synthase.Bioorganic & medicinal chemistry · 2014Article
- Design, synthesis and biological evaluation of sulfur-containing 1,1-bisphosphonic acids as antiparasitic agents.European journal of medicinal chemistry · 2013Article
- Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 2 countries.
Funding
Abstract
Linear 2-alkylaminoethyl-1,1-bisphosphonates are effective agents against proliferation of Trypanosoma cruzi , the etiologic agent of American trypanosomiasis (Chagas disease), exhibiting IC(50) values in the nanomolar range against the parasites. This activity is associated with inhibition at the low nanomolar level of the T. cruzi farnesyl diphosphate synthase (TcFPPS). X-ray structures and thermodynamic data of the complexes TcFPPS with five compounds of this family show that the inhibitors bind to the allylic site of the enzyme, with their alkyl chain occupying the cavity that binds the isoprenoid chain of the substrate. The compounds bind to TcFPPS with unfavorable enthalpy compensated by a favorable entropy that results from a delicate balance between two opposing effects: the loss of conformational entropy due to freezing of single bond rotations and the favorable burial of the hydrophobic alkyl chains. The data suggest that introduction of strategically placed double bonds and methyl branches should increase affinity substantially.
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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.